Aerobic glycolysis and tau deposition in preclinical Alzheimer disease
Research of the human brain metabolism in vivo has largely focused on total glucose use (via FDG PET) and, until recently, did not examine the use of glucose outside oxidative phosphorylation which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. This multi-tracer PET study evaluated the relationship between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO2), tau and amyloid deposition in 42 individuals, including those at preclinical and symptomatic stages of Alzheimer disease (AD). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 20, 2018 Category: Neuroscience Authors: Andrei G. Vlassenko, Brian A. Gordon, Manu S. Goyal, Yi Su, Tyler M. Blazey, Tony J. Durbin, Lars E. Couture, Jon J. Christensen, Hussain Jafri, John C. Morris, Marcus E. Raichle, Tammie L.-S. Benzinger Source Type: research
Escitalopram alleviates stress-induced Alzheimer ’s disease-like tau pathologies and cognitive deficits by reducing HPA-axis reactivity and insulin/GSK-3β signal pathway activity
Chronic stress, a causal factor for depression, can also cause cognitive impairments and tau pathology. However, whether and how the SSRI antidepressant escitalopram ameliorates these effects are still unclear. In the present study, rats were subjected to chronic mild unpredictable stress (CUS) for eight weeks. Following the initial four weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resistant) groups based on behavioral tests. Then, escitalopram (10 mg/kg i.p.) was administered for 28 days. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 19, 2018 Category: Neuroscience Authors: Chao Wu, Wei-Gang Gong, Yan-Juan Wang, Jun-Jun Sun, Hong Zhou, Zhi-Jun Zhang, Qing-Guo Ren Source Type: research
Nonlinear pattern of the emergence of white matter hyperintensity in healthy Han Chinese: an adult lifespan study
This study aimed to investigate the WMH burden across the adult lifespan and determine the interrelationships among age, WMH, and cognition. The current study included 312 healthy individuals aged 21 to 89 years who received structural magnetic resonance imaging and cognitive assessments. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 19, 2018 Category: Neuroscience Authors: Chu-Chung Huang, Albert C. Yang, Kun-Hsien Chou, Mu-En Liu, Shih-Chun Fang, Chi-Chang Chen, Shih-Jen Tsai, Ching-Po Lin Source Type: research
EEG-based neurophysiological indicators of hallucinations in Alzheimer ’s disease: comparison with dementia with Lewy bodies
We studied neurophysiological indicators of hallucinations in Alzheimer ’s disease patients with hallucinations (ADhall+), and compared them with non-hallucinating AD (ADhall-) and dementia with Lewy bodies (DLBhall+) patients. 36 matched ADhall+ and 108 ADhall-, and 29 DLBhall+ patients were selected from the Amsterdam Dementia Cohort. EEG spectral and functional con nectivity (FC) analysis (phase lag index) were performed. Quantitative and visual EEG measures were combined in a random forest algorithm to determine which EEG-based variable(s) play a role in hallucinations. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 19, 2018 Category: Neuroscience Authors: M. Dauwan, M.M.J. Linszen, A.W. Lemstra, P. Scheltens, C.J. Stam, I.E. Sommer Source Type: research
The effect of long-term treatment with coenzyme Q10 on nucleic acid modifications by oxidation in children with Down syndrome
Elevated levels of oxidative nucleic acid modifications have been proposed to be associated with some of the clinical characteristics of Down syndrome. Oral intake of coenzyme Q10 (CoQ10) improves oxidative status and shows a tendency towards protective effect on DNA oxidation in certain age groups of children with Down syndrome. Here, we demonstrate that long-term (i.e. 4 years) treatment with CoQ10 (ubiquinone) at the dosage of 4 mg/kg/day does not affect whole body DNA and RNA oxidation. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 15, 2018 Category: Neuroscience Authors: Emil List Larsen, Lucia Padella, Helle Kirstine M ørup Bergholdt, Trine Henriksen, Lucia Santoro, Orazio Gabrielli, Henrik Enghusen Poulsen, Gian Paolo Littarru, Patrick Orlando, Luca Tiano Tags: Negative results Source Type: research
Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation
Brain aging is marked by cognitive decline and susceptibility to neurodegeneration. Caloric-restriction (CR) increases neurogenesis, improves memory function, and protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital to normal CNS cellular and memory functions, and are dysregulated with aging. The beneficial effects of CR have been proposed to work through epigenetic processes, but this is largely unexplored. We therefore tested whether life-long CR prevents age-related hippocampal DNA methylation changes. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 15, 2018 Category: Neuroscience Authors: Niran Hadad, Archana Unnikrishnan, Jordan A. Jackson, Dustin R. Masser, Laura Otalora, David R. Stanford, Arlan Richardson, Willard M. Freeman Source Type: research
Degradation of alpha-synuclein by dendritic cell factor1 delays neurodegeneration and extends lifespan in Drosophila
In this study, we aimed to show that dcf1 overexpression in a PD Drosophila model significantly ameliorates impaired locomotor behavior i n third instar larvae and normalizes neuromuscular junction growth. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 13, 2018 Category: Neuroscience Authors: Shiqing Zhang, Ruili Feng, Linhua Gan, Yanhui Li, Fangfang Zhou, Shiquan Meng, Qian Li, Tieqiao Wen Source Type: research
‘Lipid Raft Aging’ in the Human Frontal Cortex During Non-Pathological Aging: Gender Influences and Potential Implications in Alzheimer’s Disease
Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared to the surrounding plasma membrane. These microstructures are associated not only with cellular signalling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer ’s disease. Using lipid rafts isolated from human frontal cortex in non-demented subjects aging 24-85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as ...
Source: Neurobiology of Aging - March 9, 2018 Category: Neuroscience Authors: Mario D íaz, Noemí Fabelo, Isidre Ferrer, Raquel Marín Source Type: research
Behavioral tagging and capture: long-term memory decline in middle-aged rats
Decline in cognitive functions, including hippocampus-dependent spatial memory, is commonly observed at a later stage of aging (e.g.> 20 month-old in rodents) and typically studied after a discrete learning event. How normal aging, particularly at an early stage, affects the modulatory aspect of memory persistence is under-investigated. Previous studies in young animals show that weak, fading memories can last longer if a modulating event, such as spatial novelty, is introduced around memory encoding. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 9, 2018 Category: Neuroscience Authors: Alexandra Gros, Szu-Han Wang Source Type: research
Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C and DDRGK1 with Parkinson ’s disease in East Asians
A recent large-scale European-originated genome-wide association data meta-analysis followed by a replication study identified six new risk loci for Parkinson ’s disease (PD), which include rs10797576/SIPA1L2, rs117896735/INPP5F, rs329648/MIR4697, rs11158026/GCH1, rs2414739/VPS13C and rs8118008/DDRGK1. However, whether these new loci are associated with PD in Asian populations remains elusive. The INPP5F is non-polymorphic in Asians. The current study a imed to understand the effects of the other five new loci in a Han Chinese population comprising 579 sporadic PD patients and 642 controls. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 9, 2018 Category: Neuroscience Authors: Ming Zou, Rui Li, Jian-Yong Wang, Ke Wang, Ya-Nan Wang, Yang Li, Fei-Xue Ji, Sheng-Nan Sun, Shi-Shi Huang, Hui-Hui Fan, Chen-Ping Huang, Xiong Zhang, Jian-Hong Zhu Source Type: research
A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer’s disease in Hong Kong Chinese population
Alzheimer ’s disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than ApoE ɛ4 contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kon g Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls. Among the genes involved in immune function, we identified a rare stop-gain variant (p.Q48X) in MLKL gene present exclusively in 6 LOA D cases. (Sour...
Source: Neurobiology of Aging - March 9, 2018 Category: Neuroscience Authors: Binbin Wang, Suying Bao, Zhigang Zhang, Xueya Zhou, Jing Wang, Yanhui Fan, Yan Zhang, Yan Li, Luhua Chen, Yizhen Jia, Jiang Li, Miaoxin Li, Wenhua Zheng, Nan Mu, Liqiu Wang, Zhe Yu, Dana SM. Wong, Yalun Zhang, Joseph Kwan, Henry Ka-Fung Mak, Amirthagowri Source Type: research
Clinical variability and onset age modifiers in an extended Belgian GRN founder family
We previously reported a GRN null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia (FTD). Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with FTD, while others had a clinical diagnosis of unspecified dementia, Alzheimer ’s dementia or Parkinson’s disease. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 9, 2018 Category: Neuroscience Authors: Eline Wauters, Sara Van Mossevelde, Kristel Sleegers, Julie van der Zee, Sebastiaan Engelborghs, Anne Sieben, Rik Vandenberghe, St éphanie Philtjens, Marleen Van den Broeck, Karin Peeters, Ivy Cuijt, Wouter De Coster, Tim Van Langenhove, Patrick Santens, Source Type: research
Genome-wide association identifies a novel locus for delirium risk
We aimed to identify common genetic variations associated with delirium through genome-wide association testing in a hospital biobank. We applied a published electronic health record based definition of delirium to identify cases of delirium, and control individuals with no history of delirium, from a biobank spanning two Boston academic medical centers. Among 6,035 individuals of Northern European ancestry, including 421 with a history of delirium, we used logistic regression to examine genome-wide association. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 9, 2018 Category: Neuroscience Authors: Thomas H. McCoy, Kamber Hart, Amelia Pellegrini, Roy H. Perlis Source Type: research
Compromise of Cortical proNGF Maturation Causes Selective Retrograde Atrophy in Cholinergic Nucleus Basalis Neurons
The degeneration of Basal Forebrain Cholinergic Neurons (BFCNs) in Alzheimer ’s disease (AD) contributes to cognitive impairment. Nerve Growth Factor (NGF) secreted in the cerebral cortex is necessary for the phenotypic maintenance of BFCNs. AD is associated with disturbances in NGF metabolism, leading to reduced mature NGF (mNGF) levels and to an accumulation of its precu rsor, proNGF. We previously described that, in rats, this neurotrophic imbalance is sufficient to induce a loss of cortical cholinergic synapses. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 8, 2018 Category: Neuroscience Authors: Simon Allard, Marie L. Jacobs, Sonia Do Carmo, A. Claudio Cuello Source Type: research
Tooth loss is associated with accelerated cognitive decline and volumetric brain differences: a population-based study
Tooth loss has been related to cognitive impairment, however its relation to structural brain differences in humans is unknown. Dementia-free participants (n= 2715) age ≥60 years were followed for up to 9 years. A sub-sample (n=394) underwent MRI at baseline. Information on tooth loss was collected at baseline and cognitive function was assessed using the Mini-Mental State Examination (MMSE) at baseline and at follow-ups. Data were analyzed using linear mixed-eff ects models and linear regression models. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 8, 2018 Category: Neuroscience Authors: Christina S. Dintica, Debora Rizzuto, Anna Marseglia, Gr égoria Kalpouzos, Anna-Karin Welmer, Inger Wårdh, Lars Bäckman, Weili Xu Source Type: research
Negative fateful life events in midlife and advanced predicted brain aging
We examined 359 men (mean age 62 years) participating in the Vietnam Era Twin Study of Aging (VETSA) to determine whether negative midlife FLEs are associated with advanced brain aging after controlling for physical, psychological and lifestyle factors. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 8, 2018 Category: Neuroscience Authors: Sean N. Hatton, Carol E. Franz, Jeremy A. Elman, Matthew S. Panizzon, Donald J. Hagler, Christine Fennema-Notestine, Lisa T. Eyler, Linda K. McEvoy, Michael J. Lyons, Anders M. Dale, William S. Kremen Source Type: research
Deuterated polyunsaturated fatty acids reduce brain lipid peroxidation and hippocampal amyloid β-peptide levels, without discernable behavioral effects in an APP/PS1 mutant transgenic mouse model of Alzheimer's disease
Alzheimer's disease (AD) involves progressive deposition of amyloid β-peptide (Aβ), synapse loss and neuronal death, which occur in brain regions critical for learning and memory. Considerable evidence suggests that lipid peroxidation contributes to synaptic dysfunction and neuronal degeneration, both upstream and downstream of Aβ pathology. Recent findings sugge st that lipid peroxidation can be inhibited by replacement of polyunsaturated fatty acids (PUFA) with isotope-reinforced (deuterated) PUFA (D-PUFA), and that D-PUFA can protect neurons in experimental models of Parkinson's disease. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 5, 2018 Category: Neuroscience Authors: Sophia M. Raefsky, Ran Furman, Ginger Milne, Erik Pollock, Paul Axelsen, Mark P. Mattson, Mikhail S. Shchepinov Source Type: research
Motor coordination and synaptic plasticity deficits are associated with increased cerebellar activity of NAPDH oxidase, CAMKII, and PKC at pre-plaque stage in the TgCRND8 mouse model of Alzheimer' ’s disease.
Numerous studies indicate that cerebellum undergoes structural and functional neurodegenerative changes in Alzheimer' ’s disease. The purpose of this study was to examine the extent of cerebellar alterations at early, pre-plaque stage of the pathology in TgCRND8 mice through behavioral, electrophysiological and molecular analysis. Balance beam test and foot-printing analysis revealed significant motor coordinatio n and balance deficits in 2-month-old TgCRND8 mice compared to their littermates. Patch-clamp recordings performed on cerebellar slices of Tg mice showed synaptic plasticity deficit and loss of noradrenergic...
Source: Neurobiology of Aging - March 5, 2018 Category: Neuroscience Authors: Roberto Russo, Fabio Cattaneo, Pellegrino Lippiello, Claudia Cristiano, Fabio Zurlo, Martina Castaldo, Carlo Irace, Tiziana Borsello, Rita Santamaria, Rosario Ammendola, Antonio Calignano, Maria Concetta Miniaci Source Type: research
Cerebral microhemorrhages due to traumatic brain injury and their effects upon the aging human brain
Although cerebral microbleeds (CMBs) are frequently associated with traumatic brain injury (TBI), their effects upon clinical outcome after TBI remain controversial and poorly-understood, particularly in older adults. Here we (A) highlight major challenges and opportunities associated with studying the effects of TBI-mediated CMBs, (B) review the evidence on their potential effects upon cognitive and neural outcome as a function of age at injury, and (C) suggest priorities for future research on understanding the clinical implications of CMBs. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 5, 2018 Category: Neuroscience Authors: Andrei Irimia, John D. Van Horn, Paul M. Vespa Source Type: research
Impact of insulin signaling and proteasomal activity on physiological output of a neuronal circuit in aging D. melanogaster
The insulin family of growth factors plays an important role in development and function of the nervous system. Reduced insulin and insulin-growth-factor signalling (IIS), however, can improve symptoms of neurodegenerative diseases in laboratory model organisms and protect against age-associated decline in neuronal function. Recently, we showed that chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila Giant Fiber escape response circuit (Augustin et al., 2017). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 5, 2018 Category: Neuroscience Authors: Hrvoje Augustin, Kieran McGourty, Marcus J. Allen, Jennifer Adcott, Chi Tung Wong, Emmanuel Boucrot, Linda Partridge Source Type: research
Longitudinal Accrual of Neocortical Amyloid Burden Is Associated with Microstructural Changes of the Fornix in Cognitively-Normal Adults
The fornix and parahippocampal cingulum are two major limbic tracts in the core memory network of the hippocampus. Although these fiber tracts are known to degrade with Alzheimer ’s disease (AD), little is known about their vulnerability in the asymptomatic phase of AD. In this longitudinal study of cognitively-normal adults, we assessed amyloid-beta (Aβ) plaques using positron emission tomography (PET) and white matter microstructure using Diffusion Tensor Imaging (DTI). We found that an increase of neocortical Aβ burden over time was associated with an increase of radial diffusivity in the fornix but not ...
Source: Neurobiology of Aging - February 28, 2018 Category: Neuroscience Authors: Zhuang Song, Michelle E. Farrell, Xi Chen, Denise C. Park Source Type: research
Chromogranin A levels in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis
Chromogranin A (CgA) is a protein found in large dense-core vesicles of neuroendocrine cells and neurons and regulating secretion. A relevance to ALS was suggested as its overexpression accelerates disease onset in model systems and it interacts with mutant forms of SOD1. Recently, increased cerebrospinal fluid (CSF) CgA levels have been reported in ALS patients relative to controls. With the aim of confirming this finding, we measured CgA and phosphorylated neurofilament heavy chain (pNFH), an established ALS biomarker, in the CSF of 32 ALS patients and 32 disease controls. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 27, 2018 Category: Neuroscience Authors: Federico Verde, Petra Steinacker, Patrick Oeckl, Jochen H. Weishaupt, Angela Rosenbohm, Vincenzo Silani, Albert C. Ludolph, Markus Otto Tags: Negative results Source Type: research
Repression of adenosine triphosphate binding cassette transporter ABCG2 by estrogen increases intracellular glutathione in brain endothelial cells following ischemic reperfusion injury
This study was aimed to define the role of ABCG2 in estrogen-mediated neuroprotection against ischemic injury. ABCG2 protein levels before and after ischemic stroke were increased in the brain of female mice by ovariectomy, which were reversed by estrogen replacement. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 27, 2018 Category: Neuroscience Authors: Jin A. Shin, Sae Im Jeong, Hye Won Kim, Gyeonghui Jang, Dong-Ryeol Ryu, Young-Ho Ahn, Ji Ha Choi, Youn-Hee Choi, Eun-Mi Park Source Type: research
Photobiomodulation reduces gliosis in the basal ganglia of aged mice
This study explored the effects of long-term photobiomodulation on the glial and neuronal organisation in the striatum of aged mice. Mice aged 12 months were pre-treated with photobiomodulation (670nm) for 20 minutes per day, commencing at 5 months old and continued for 8 months. We had two control groups, young at 3 and aged at 12 months old; these mice received no treatment. Brains were aldehyde-fixed and processed for immunohistochemistry with various glial and neuronal markers. We found a clear reduction in glial cell number, both astrocytes and microglia, in the striatum after photobiomodulation in aged mice. (Source:...
Source: Neurobiology of Aging - February 26, 2018 Category: Neuroscience Authors: Nabil El Massri, Tobias W. Weinrich, Jaimie Hoh Kam, Glen Jeffery, John Mitrofanis Source Type: research
Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis.
This study identifies miRNAs that are altered in ALS that may serve as potentials biomarkers. PMID: 29458840 [PubMed - in process] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 22, 2018 Category: Geriatrics Authors: Matamala JM, Arias-Carrasco R, Sanchez C, Uhrig M, Bargsted L, Matus S, Maracaja-Coutinho V, Abarzua S, van Zundert B, Verdugo R, Manque P, Hetz C Tags: Neurobiol Aging Source Type: research
Early-life stress induces cognitive disorder in middle-aged mice.
In this study, we used maternal deprivation (MD) to examine the cognitive function in middle-aged mice using a touchscreen-equipped operant chamber. In the visual-discrimination task, the aged (∼1.4 years old) control mice could accurately learn to discriminate between different visual stimuli. In contrast, the correct response rate of aged MD mice increased to ∼60% by day 10; it was still significantly lower than that of the control mice (85%). In the hippocampus of aged MD mice, the expression level of the N-methyl-d-aspartate receptor subunit GluN1 decreased significantly as compared to that in control mice...
Source: Neurobiology of Aging - February 22, 2018 Category: Geriatrics Authors: Yajima H, Haijima A, Khairinisa MA, Shimokawa N, Amano I, Takatsuru Y Tags: Neurobiol Aging Source Type: research
Cognitive response to fish oil, blueberry, and combined supplementation in older adults with subjective cognitive impairment.
Abstract Given evidence that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and anthocyanin-rich blueberries provide neurocognitive benefit, we investigated long-term supplementation in older adults with cognitive complaints. In a 24-week randomized, double-blind, placebo-controlled trial, elderly men and women received daily fish oil (FO) or blueberry (BB) or both. Diet records confirmed that participants reduced background consumption of EPA, DHA, and anthocyanins as prescribed. Erythrocyte EPA + DHA composition increased in the FO groups (p = 0.0001). Total urinary anthocyanins did not diffe...
Source: Neurobiology of Aging - February 22, 2018 Category: Geriatrics Authors: McNamara RK, Kalt W, Shidler MD, McDonald J, Summer SS, Stein AL, Stover AN, Krikorian R Tags: Neurobiol Aging Source Type: research
Neurodegenerative Disease and Cognitive Retest Learning
Retest learning impacts estimates of cognitive aging, but its bases are uncertain. Here we test the hypothesis that dementia related neurodegeneration impairs retest learning. Older persons without cognitive impairment at enrollment (n=567) had annual cognitive testing for a mean of 11 years, died, and had a neuropathologic examination to quantify 5 neurodegenerative pathologies. Change point models were used to divide cognitive trajectories into an early retest sensitive component and a later component less sensitive to retest. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 22, 2018 Category: Neuroscience Authors: Robert S. Wilson, Ana W. Capuano, Lei Yu, Jingyun Yang, Namhee Kim, Sue E. Leurgans, Melissa Lamar, Julie A. Schneider, David A. Bennett, Patricia A. Boyle Source Type: research
APOE genotype modifies the association between central arterial stiffening and cognition in older adults
This study tested the interaction between arterial stiffening and an AD genetic risk factor (APOE genotype) on cognition among older adults. Vanderbilt Memory& Aging Project participants with normal cognition (NC, n=162, 72 ±7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (MCI, n=121, 73±8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 20, 2018 Category: Neuroscience Authors: Francis E. Cambronero, Dandan Liu, Jacquelyn E. Neal, Elizabeth E. Moore, Katherine A. Gifford, James G. Terry, Sangeeta Nair, Kimberly R. Pechman, Katie E. Osborn, Timothy J. Hohman, Susan P. Bell, J. David Sweatt, Thomas J. Wang, Joshua A. Beckman, John Source Type: research
Alterations in glutamatergic signalling contribute to the decline of circadian photoentrainment in aged mice.
Robust physiological circadian rhythms form an integral part of wellbeing. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/ disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioural activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 20, 2018 Category: Neuroscience Authors: S.M. Biello, D.R. Bonsall, L.A. Atkinson, P.C. Molyneux, M.E. Harrington, G.S. Lall Source Type: research
Predominant subcortical accumulation of 18F-flortaucipir binding in behavioral variant frontotemporal dementia
In this study, we sought to investigate 18F-flortaucipir binding patterns and their correlates in clinically-diagnosed bvFTD patients by comparing with results for Alzheimer ’s disease (AD) patients. We enrolled 20 bvFTD, 20 AD and 20 age-matched healthy subjects who underwent neuropsychological tests, magnetic resonance imaging, and tau positron emission tomography scans with 18F-flortaucipir. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 20, 2018 Category: Neuroscience Authors: Hanna Cho, Sang Won Seo, Jae Yong Choi, Hye Sun Lee, Young Hoon Ryu, Myung Sik Lee, Duk L. Na, Hee Jin Kim, Chul Hyoung Lyoo Source Type: research
The Neurochemical Basis of the Contextual Interference Effect
Efficient practice organization maximizes learning outcome. Although randomization of practice as compared to blocked practice damages training performance, it boosts retention performance, an effect called contextual interference (CI). Motor learning modulates the GABAergic (gamma-aminobutyric acid) system within the sensorimotor cortex (SM), however, it is unclear whether different practice regimes differentially modulate this system and whether this is impacted by aging. Young and older participants were trained on three variations of a visuomotor task over three days, following either blocked or random practice schedul...
Source: Neurobiology of Aging - February 19, 2018 Category: Neuroscience Authors: Sima Chalavi, Lisa Pauwels, Kirstin-Friederike Heise, Hamed Zivariadab, Celine Maes, Nicolaas A.J. Puts, Richard A.E. Edden, Stephan P. Swinnen Source Type: research
The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging
Levels of insulin-like growth factor (IGF)-1, IGF binding protein (IGFBP)-3, and their ratio in the blood may be useful for monitoring those at risk of cognitive and functional decline. However, the association between IGF measures and functional and cognitive outcomes has been mixed, and the associations may vary by sex. The present study investigated the cross-sectional, sex-specific associations between serum measures total IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio, gait speed, and cognition in 1,320 cognitively unimpaired participants aged 50-95 enrolled in the Mayo Clinic Study of Aging. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 19, 2018 Category: Neuroscience Authors: Alexandra M.V. Wennberg, Clinton E. Hagen, Mary M. Machulda, John H. Hollman, Rosebud O. Roberts, David S. Knopman, Ronald C. Petersen, Michelle M. Mielke Source Type: research
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia
We investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1066 unaffected control individuals, we identified 5 patient-only nonsynonymous rare variants in SORT1. Rare variant burden analysis showed a significant increase in rare coding variants in patients compared to control individuals (p = 0.04), particularly in the β-propeller domain (p = 0.04), with 2 rare variants located in the predicted binding site for...
Source: Neurobiology of Aging - February 17, 2018 Category: Neuroscience Authors: St éphanie Philtjens, Sara Van Mossevelde, Julie van der Zee, Eline Wauters, Lubina Dillen, Mathieu Vandenbulcke, Rik Vandenberghe, Adrian Ivanoiu, Anne Sieben, Christiana Willems, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Barbara Borroni, Alessa Source Type: research
Age-related pathology after adenoviral overexpression of the leucine-rich repeat kinase 2 in the mouse striatum
In this study we compared the effect of striatal injection of high-capacity adenoviral vectors expressing either kinase-overactive LRRK2 with the familial G2019S mutation or a kinase-inactive LRRK2 variant in young and old C57BL/6J mice. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 17, 2018 Category: Neuroscience Authors: Astrid Kritzinger, Boris Ferger, Frank Gillardon, Birgit Stierstorfer, Gerald Birk, Stefan Kochanek, Thomas Ciossek Source Type: research
Rare non-synonymous variants in SORT1 are associated with increased risk for frontotemporal dementia
We investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1,066 unaffected control individuals, we identified five patient-only non-synonymous rare variants in SORT1. Rare variant burden analysis showed a significant increase in rare coding variants in patients compared to control individuals (p=0.04), particularly in the β-propeller domain (p=0.04), with two rare variants located in the predicted binding site for GRN (p=0.001...
Source: Neurobiology of Aging - February 17, 2018 Category: Neuroscience Authors: St éphanie Philtjens, Sara Van Mossevelde, Julie van der Zee, Eline Wauters, Lubina Dillen, Mathieu Vandenbulcke, Rik Vandenberghe, Adrian Ivanoiu, Anne Sieben, Christiana Willems, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Barbara Borroni, Alessa Source Type: research
Associations of Carotid Arterial Compliance and White Matter Diffusion Metrics during Midlife: Modulation by Sex
Sex differences in cerebral white matter (WM) aging have been debated extensively over the past two decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on white matter (WM) microstructure differ between sexes. Artery elasticity via carotid artery compliance (CAC) and WM diffusion metrics via diffusion tensor image derived fractional anisotropy (FA) and mean diffusivity (MD) were measured in 155 (87 females) middle-aged (40-62 years) adults. Males demonstrated poorer water diffusion metrics in WM than women in the corpus callosum body, cingulum, and cingulum (hippocampa...
Source: Neurobiology of Aging - February 17, 2018 Category: Neuroscience Authors: Evan P. Pasha, Alex C. Birdsill, Stephanie Oleson, Hirofumi Tanaka, Andreana P. Haley Source Type: research
Mutation analysis of CHCHD2 and CHCHD10 in Italian patients with mitochondrial myopathy
Mutations in CHCHD2 and CHCHD10 were recently reported in a broad spectrum of neurodegenerative diseases, e.g. Parkinson ’s disease, amyotrophic lateral sclerosis, frontotemporal dementia or mitochondrial myopathy (MM). The aim of the study was to evaluate the prevalence of CHCHD2 and CHCHD10 mutations in Italian MM patients without mitochondrial DNA mutations. The coding regions of CHCHD2 and CHCHD10 were sequenced in 62 MM patients. None of the patients showed CHCHD2 mutations, whereas one sporadic MM patient carried a homozygous Pro96Thr substitution in CHCHD10. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 15, 2018 Category: Neuroscience Authors: Elisa Rubino, Ming Zhang, Tiziana Mongini, Silvia Boschi, Liliana Vercelli, Alessandro Vacca, Flora Govone, Annalisa Gai, Maria Teresa Giordana, Mark Grinberg, Ekaterina Rogaeva, Innocenzo Rainero Source Type: research
Identification of Rare Genetic Variants In Italian Patients With Dementia By Targeted Gene Sequencing
In this study, we conducted targeted sequencing in 246 clinically heterogeneous patients, mainly with early-onset and/or familial neurodegenerative dementia, using a custom-designed Next Generation Sequencing (NGS) panel covering 27 genes known to harbor mutations that can cause different types of dementia, in addition to the detection of C9orf72 repeat expansions. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 12, 2018 Category: Neuroscience Authors: Anna Bartoletti-Stella, Simone Baiardi, Michelangelo Stanzani-Maserati, Silvia Piras, Paolo Caffarra, Alberto Raggi, Roberta Pantieri, Sara Baldassari, Leonardo Caporali, Samir Abu-Rumeileh, Simona Linarello, Rocco Liguori, Piero Parchi, Sabina Capellari Source Type: research
Multimodal Neuroimaging and Behavioral Assessment of SNCA Polymorphism rs356219 in Older Adults
The single nucleotide polymorphism rs356219 in the α-synuclein (SNCA) gene has been shown to significantly contribute to an earlier age at onset of Parkinson’s disease (PD), regulate SNCA expression in PD-brain regions, blood and plasma. Here, we used multimodal MRI to study healthy adults with and without the rs356219 risk genotype. Motor and co gnitive tests were administered and all participants underwent functional and structural MRI. Imaging analyses included: 1) task-based functional MRI, 2) task-based functional connectivity, 3) free-water diffusion MRI of the substantia nigra, 4) voxel-based morphometry...
Source: Neurobiology of Aging - February 10, 2018 Category: Neuroscience Authors: Roxana G. Burciu, Rachael D. Seidler, Priyank Shukla, Mike A. Nalls, Andrew B. Singleton, Michael S. Okun, David E. Vaillancourt Source Type: research
White matter hyperintensities and vascular risk factors in monozygotic twins
We examined in a monozygotic twin sample whether the association between vascular risk and WMH is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age=70 ±7), including 94 complete pairs. Regional WMH load was estimated using an automated algorithm. Vascular risk was summarized with the Framingham score. The within twin pair correlation for total WMH was 0.76 and for Framingham score 0.77. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 10, 2018 Category: Neuroscience Authors: Mara ten Kate, Carole H. Sudre, Anouk den Braber, Elles Konijnenberg, Michel G. Nivard, M. Jorge Cardoso, Philip Scheltens, S ébastien Ourselin, Dorret I. Boomsma, Frederik Barkhof, Pieter Jelle Visser Source Type: research
Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson ’s disease
Dopaminergic medications improve the motor symptoms of Parkinson ’s disease (PD), but their effect on response inhibition, a critical executive function, remains unclear. Previous studies primarily enrolled patients in more advanced stages of PD, when dopaminergic medication loses efficacy, and patients were typically on multiple medications. Here, we recruited 21 patients in early-stage PD on levodopa monotherapy and 37 age-matched controls to perform the stop-signal task during fMRI. In contrast to previous studies reporting null effects in more advanced PD, levodopa significantly improved response inhibition perfo...
Source: Neurobiology of Aging - February 10, 2018 Category: Neuroscience Authors: Peter Manza, Guy Schwartz, Mala Masson, Sarah Kann, Nora D. Volkow, Chiang-shan R. Li, Hoi-Chung Leung Source Type: research
Genetic markers of dopaminergic transmission predict performance for older males but not females
We examined four SNPs involved in dopaminergic metabolism: BDNF (Val66Met), DRD3 (Ser9Gly), DBH (C>T), and COMT (Val158Met) for their relationship to motor and cognitive function in healthy older adults (n = 4,605 and n = 7,331) who participated in the U.S. Health and Retirement Study. Individuals with genotypes associated with reduced dopamine metabolism exhibited poorer balance and memory. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 10, 2018 Category: Neuroscience Authors: Kathleen E. Hupfeld, David E. Vaillancourt, Rachael D. Seidler Source Type: research
Longitudinal and cross-sectional structural MRI correlates of AV-1451 uptake
We examined the relationship between in-vivo estimates of tau deposition as measured by 18F-AV-1451 tau PET imaging and cross-sectional cortical thickness as well as rates of antecedent cortical thinning measured from MRI in individuals with and without evidence of cerebral amyloid in 63 participants from the Alzheimer ’s Disease Neuroimaging Initiative study, including 32 cognitively normal individuals (mean age 74 years), 27 patients with mild cognitive impairment (MCI, mean age 76.8 years) and 4 patients diagnosed with Alzheimer’s disease (AD, mean age 80 years). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 9, 2018 Category: Neuroscience Authors: Sandhitsu R. Das, Long Xie, Laura E.M. Wisse, Ranjit Ittyerah, Nicholas J. Tustison, Bradford C. Dickerson, Paul A. Yushkevich, David A. Wolk, Alzheimer ’s Disease Neuroimaging Initiative Source Type: research
Contributions of micro- and macrovascular disease to reduced substantia innominata volume and cognitive deficits in Alzheimer ’s disease
The relationships between cholinergic system damage and cerebrovascular disease are not entirely understood. Here we investigate associations between atrophy of the substantia innominata (SI; the origin of cortical cholinergic projections) and measures of large and small vessel disease; specifically, elongation of the juxtaposed internal carotid artery termination and Cholinergic Pathways Hyperintensity scores (CHIPS). The study consisted of 105 patients with Alzheimer ’s disease (AD), subcortical ischemic vasculopathy (SIV), and elderly controls. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 9, 2018 Category: Neuroscience Authors: Gurpreet Jaswal, Walter Swardfager, Fu-qiang Gao, Sean Nestor, Anoop Ganda, Hugo Cogo-Moreira, Demetrios Sahlas, Donald T. Stuss, Alan Moody, Sandra E. Black Source Type: research
Alterations in cholesterol metabolism –related genes in sporadic Alzheimer's disease
Genome-wide association studies have identified several cholesterol metabolism –related genes as top risk factors for late-onset Alzheimer's disease (LOAD). We hypothesized that specific genetic variants could act as disease-modifying factors by altering the expression of those genes. Targeted association studies were conducted with available genomic, transcriptomic, proteom ic, and histopathological data from 3 independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Quebec Founder Population (QFP), and the United Kingdom Brain Expression Consortium (UKBEC). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 8, 2018 Category: Neuroscience Authors: Cynthia Picard, C édric Julien, Josée Frappier, Justin Miron, Louise Théroux, Doris Dea, United Kingdom Brain Expression Consortium and for the Alzheimer's Disease Neuroimaging Initiative, John C.S. Breitner, Judes Poirier Source Type: research
Alterations in cholesterol metabolism-related genes in sporadic Alzheimer ’s disease
Genome-wide association studies have identified several cholesterol metabolism-related genes as top risk factors for late-onset Alzheimer ’s disease (LOAD). We hypothesized that specific genetic variants could act as disease-modifying factors by altering the expression of those genes. Targeted association studies were conducted with available genomic, transcriptomic, proteomic and histopathological data from three independent cohort s: the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Quebec Founder Population (QFP) and the United Kingdom Brain Expression Consortium (UKBEC). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - February 8, 2018 Category: Neuroscience Authors: Cynthia Picard, C édric Julien, Josée Frappier, Justin Miron, Louise Théroux, Doris Dea, United Kingdom Brain Expression Consortium and for the Alzheimer’s Disease Neuroimaging Initiative, John C.S. Breitner, Judes Poirier Source Type: research