Postmortem Brain MRI Is Related to Cognitive Decline, Independent of Cerebral Vessel Disease in Older Adults
The purpose of this study was to determine whether metrics of brain tissue integrity derived from postmortem MRI are associated with late life cognitive decline, independent of cerebral vessel disease. Using data from 554 older adults, we employed voxelwise regression to identify regions where the postmortem MRI transverse relaxation rate constant R2 was associated with the rate of decline in global cognition. We then used linear mixed models to investigate the association between a composite R2 measure and cognitive decline, controlling for neuropathology including three indices of vessel disease: atherosclerosis, arterio...
Source: Neurobiology of Aging - May 23, 2018 Category: Neuroscience Authors: Robert J. Dawe, Lei Yu, Julie A. Schneider, Konstantinos Arfanakis, David A. Bennett, Patricia A. Boyle Source Type: research

Functional Networks Underlying Item and Source Memory: Shared and Distinct Network Components and Age-Related Differences
Whereas the medial temporal lobes (MTL) are critical for both item memory (IM) and source memory (SM), lateral prefrontal cortex (LatPFC) and posterior parietal cortex (PPC) play a greater role during SM than IM. It is unclear, however, how these differences translate into shared and distinct IM vs. SM network components and how these network components vary with age. Within a sample of younger adults (YAs; n=15, Mage=19.5 years) and older adults (OAs; n=40, Mage=68.6 years), we investigated the functional networks underlying IM and SM. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 21, 2018 Category: Neuroscience Authors: Zachary A. Monge, Matthew L. Stanley, Benjamin R. Geib, Simon W. Davis, Roberto Cabeza Source Type: research

The effect of APOE genotype on Alzheimer ’s disease risk is influenced by sex and DHA status
An APOE- ε4 genotype is the strongest common genetic determinant of Alzheimer’s disease (AD). The pleiotropic nature of apolipoprotein E, has made elucidation of the aetiological basis difficult to establish which is further complicated by the fact that the penetrance of the APOE- ε4 allele is modulated by sex, age, and nutrition.A greater metabolic consequence of the APOE- ε4 allele is likely to contribute to the fact that two thirds of AD patients are female. A higher tissue status of the marine n-3 fatty acid docosahexaenoic acid (DHA), is associated with a lower AD risk. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 21, 2018 Category: Neuroscience Authors: Matthew Pontifex, David Vauzour, Anne-Marie Minihane Source Type: research

Aging of human alpha rhythm
The changes of the posterior alpha rhythm (AR) in electroencephalogram (EEG) are among the most pronounced phenomena related to brain aging in humans. They include AR slowing (Ba şar, 2012; Clark et al., 2004; Gaál et al., 2010; Hubbard et al., 1976; Lodder and van Putten, 2011; Markand, 1986; Peltz et al., 2010; Shigeta et al., 1995; Van Sweden et al., 1999; Wang and Busse, 1969), reduction of its power (Lodder and van Putten, 2011; Vysata et al., 2012), a shift of AR sou rces in the posterior-to-anterior direction (Babiloni et al., 2006; Niedermeyer, 1997; Rossini et al., 2006), and the declining AR reactivity (G...
Source: Neurobiology of Aging - May 21, 2018 Category: Neuroscience Authors: Maria G. Knyazeva, Elham Barzegaran, Vladimir Y. Vildavski, Jean-Fran çois Demonet Source Type: research

Age-Related Differences in Striatal, Medial Temporal, and Frontal Involvement During Value-Based Decision Processing
Appropriate neural representation of value and application of decision strategies are necessary to make optimal investment choices in real life. Normative human aging alters neural selectivity and control processing in brain regions implicated in value-based decision processing including striatal, medial temporal, and frontal areas. However, the specific neural mechanisms of how these age-related functional brain changes modulate value processing in older adults remain unclear. Here, young and older adults performed a lottery-choice functional magnetic resonance imaging experiment in which probabilities of winning differen...
Source: Neurobiology of Aging - May 21, 2018 Category: Neuroscience Authors: Yu-Shiang Su, Jheng-Ting Chen, Yong-Jheng Tang, Shu-Yun Yuan, Anna C. McCarrey, Joshua Oon Soo Goh Source Type: research

[18F]FMPEP-d2 PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer ’s disease
Contradictory findings on the role of the type 1 cannabinoid receptor (CB1R) during the pathogenesis of Alzheimer ’s disease (AD) have been reported. Here, we evaluated the CB1R brain profile in an AD mouse model using longitudinal positron emission tomography (PET) with an inverse agonist for CB1R, [18F]FMPEP-d2. APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 month s of age, accompanied by brain autoradiography, western blot, and CB1R immunohistochemistry with additional mice. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 18, 2018 Category: Neuroscience Authors: Jatta S. Takkinen, Francisco R. L ópez-Picón, Anna K. Kirjavainen, Rea Pihlaja, Anniina Snellman, Tamiko Ishizu, Eliisa Löyttyniemi, Olof Solin, Juha O. Rinne, Merja Haaparanta-Solin Source Type: research

Independent effects of age and levodopa on reversal learning in healthy volunteers
The dopamine overdose hypothesis has provided an important theoretical framework for understanding cognition in Parkinson ’s disease. It posits that effects of dopaminergic therapy on cognition in Parkinson’s disease depend on baseline dopamine levels in brain regions that support different functions. Whereas functions performed by more severely dopamine-depleted brain regions improve with medication, those associa ted with less dopamine deficient areas are actually worsened. It is presumed that medication-related worsening of cognition owes to dopamine overdose. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 18, 2018 Category: Neuroscience Authors: Andrew Vo, Ken N. Seergobin, Penny A. MacDonald Source Type: research

The relation between Scrabble © Expertise and Brain Aging as Measured with EEG Brain Signal Variability
Recent empirical work suggests that the dynamics of brain function, as measured by brain signal variability, differs between younger and older adults. We extended this work by examining how the relationship between brain signal variability and age is altered in the context of expertise. We recorded electroencephalography (EEG) from Scrabble experts and controls during a visual word recognition task. To measure variability, we used multiscale entropy (MSE), which emphasizes the way brain signals behave over a range of timescales, and can differentiate the variability of a complex system (the brain) from a purely random syst...
Source: Neurobiology of Aging - May 18, 2018 Category: Neuroscience Authors: Hongye Wang, Penny M. Pexman, Gary Turner, Filomeno Cortese, Andrea B. Protzner Source Type: research

Loss of Trem2 in microglia leads to widespread disruption of cell co-expression networks in mouse brain
We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 17, 2018 Category: Neuroscience Authors: Guillermo Carbajosa, Karim Malki, Nathan Lawless, Hong Wang, John W. Ryder, Eva Wozniak, Kristie Wood, Charles A. Mein, Richard J.B. Dobson, David A. Collier, Michael J. O ’Neill, Angela K. Hodges, Stephen J. Newhouse Source Type: research

Targeted next generation sequencing reveals novel and rare variants in Indian patients with Amyotrophic Lateral Sclerosis
In this study, we used targeted next-generation sequencing (NGS) to analyze 25 ALS-associated genes in a cohort of 154 Indian ALS patients. We identified known pathogenic mutations in SOD1 (G148D; H44R), TARDBP (M337V; N267S), DAO (R199Q) and ANG (K41I). In addition, we also identified 7 potentially pathogenic missense variants that have not been previously reported in ALS patients; this includes 3 novel variants (OPTN: K489E, DAO: E121K and SETX: L2163V) that are not reported in large population databases and 4 rare variants (CHMP2B: E45K, SQSTM1: G262R and P438L, ERBB4:R103H) with a minor allele frequency (MAF) of (Sourc...
Source: Neurobiology of Aging - May 17, 2018 Category: Neuroscience Authors: Priyam Narain, Ashutosh Pandey, Shruti Gupta, James Gomes, Rohit Bhatia, Perumal Vivekanandan Source Type: research

No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients
We evaluated the genetic contribution of the T cell-restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total five rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only one missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a CADD score of 11.42. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Yalda Baradaran-Heravi, Lubina Dillen, Hung Phuoc Nguyen, Sara Van Mossevelde, Jonathan Baets, Peter De Jonghe, Sebastiaan Engelborghs, Peter P. De Deyn, Mathieu Vandenbulcke, Rik Vandenberghe, Philip Van Damme, Patrick Cras, Eric Salmon, Matthis Synofzik Tags: Negative results Source Type: research

A simple and clinically relevant combination of neuroimaging and functional indexes for the identification of those at highest risk of Alzheimer ’s disease
The current challenge in clinical practice is to identify those with mild cognitive impairment (MCI) who are at greater risk of Alzheimer ’s disease (AD) conversion in the near future. The aim of this study was to assess a clinically practical new hippocampal index –hippocampal volume normalized by cerebellar volume (Hippocampus to Cerebellum volume Ratio; HCCR) used alone or in combination with scores on the mini mental state exa mination (MMSE), as a predictor of conversion from MCI to AD. The predictive value of the HCCR was also contrasted to that of the hippocampal volume to intracranial volume (ICV) ratio...
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Hossein Tabatabaei-Jafari, Erin Walsh, Marnie E. Shaw, Nicolas Cherbuin, Alzheimer ’s Disease Neuroimaging Initiative (ADNI) Source Type: research

Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin
The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral (SC)-CA1 synapses during ageing are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of NMDA receptor-dependent long term depression (LTD) at adult (12-24 week old) TA-CA1 synapses. Leptin-induced LTD requires activation of canonical JAK2-STAT3 signalling and removal of GluA1-containing AMPA receptors from synapses. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Gemma McGregor, Leigh Clements, Adham Farah, Andrew J. Irving, Jenni Harvey Source Type: research

Pooled-DNA target sequencing of Parkinson genes reveals novel phenotypic associations in Spanish population
Eighteen PARK loci and several susceptibility genes have been related to Parkinson ’s disease (PD). However, most studies focus on single genes in small PD series. Our aim was to establish the genetic background of a large Spanish PD sample. Pooled-DNA target sequencing of seven major PD genes (SNCA, PARK2, PINK1, DJ-1, LRRK2, GBA, and MAPT) was performed in 562 PD cases. Forty- four variants were found among 114 individuals (20.28%, p (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Monica Diez-Fairen, Bruno A. Benitez, Sara Ortega-Cubero, Oswaldo Lorenzo-Betancor, Carlos Cruchaga, Elena Lorenzo, Lluis Samaranch, Maria Carcel, Jose A. Obeso, Maria Cruz Rodriguez-Oroz, Miquel Aguilar, Francisco Coria, Maria A. Pastor, Pau Pastor Source Type: research

Frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese patients with amyotrophic lateral sclerosis
Mutation frequency of the two main Amyotrophic Lateral Sclerosis (ALS)-related genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n=371) and recorded demographic and clinical features.Familial ALS (FALS) was disclosed in 11.6% of patients. Mutations in either SOD1 or C9orf72 were found in 9.2% of patients and accounted for 40% of FALS and 5.2% of sporadic ALS (SALS). SOD1 mutations were rare (0.83%), but a novel and probably disease-causing mutation was identified: p.Ala152Pro (c.457G>C). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Marta Gromicho, Susana Pinto, Eugeniu Gisca, Ana Catarina Pronto-Laborinho, Mamede de Carvalho Source Type: research

Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway
Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer ’s and Parkinson’s diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing do paminergic alterations in diabetes with age, the goal of this study was to characterize the state of two critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-te...
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Justine Renaud, Valentina Bassareo, Jimmy Beaulieu, Annalisa Pinna, Michele Schlich, Carole Lavoie, Daniela Murtas, Nicola Simola, Maria-Grazia Martinoli Source Type: research

Evaluating the Causality of Novel Sequence Variants in the Prion Protein Gene by Example
The estimation of pathogenicity and penetrance of novel prion protein gene (PRNP) variants presents significant challenges, particularly in the absence of family history, which precludes the application of Mendelian segregation. Moreover, the ambiguities of prion disease pathophysiology renders conventional in silico predictions inconclusive. Here we describe two patients with rapid cognitive decline progressing to akinetic mutism and death within 10 weeks of symptom onset, both of whom possessed the novel T201S variant in PRNP. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 14, 2018 Category: Neuroscience Authors: Tze How Mok, Carolin Koriath, Zane Jaunmuktane, Tracy Campbell, Susan Joiner, Jonathan D.F. Wadsworth, Laszlo L.P. Hosszu, Sebastian Brandner, Ambereen Parvez, Thomas Clement Truelsen, Eva L øbner Lund, Romi Saha, John Collinge, Simon Mead Source Type: research

Cover 2: Editorial Advisory Board
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 13, 2018 Category: Neuroscience Source Type: research

Contents Continued
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 13, 2018 Category: Neuroscience Source Type: research

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(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 13, 2018 Category: Neuroscience Source Type: research

Association of Telomere Length with General Cognitive Trajectories: a Meta-Analysis of Four Prospective Cohort Studies
To investigate the association of telomere length with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging and the Health and Retirement Study in the US. Telomere length was measured at baseline, while general cognitive ability was assessed repeatedly up to seven occasions. Latent growth curve models were used to examine the associations. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 11, 2018 Category: Neuroscience Authors: Yiqiang Zhan, Mark S. Clements, Rosebud O. Roberts, Maria Vassilaki, Brooke R. Druliner, Lisa A. Boardman, Ronald C. Petersen, Chandra A. Reynolds, Nancy L. Pedersen, Sara H ägg Source Type: research

Do diurnal cortisol levels mediate the association between sleep disturbances and cognitive impairment?
Previous research found an association between sleep disturbances and cognitive deficits on the one hand, and between increased cortisol levels and poor cognitive performance on the other hand. We hypothesized that cortisol may, at least partially, mediate the link between sleep disturbances and cognitive impairment. We analyzed data from 440 non-demented subjects aged ≥65 years (72.4±4.5 y.o, 55.7% women) participating at the population-based Colaus/PsyColaus study, who underwent cognitive evaluation, complete polysomnography and cortisol measures during the day. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 10, 2018 Category: Neuroscience Authors: Jos é Haba-Rubio, Sami Ouanes, Yannick Franc, Pedro Marques Vidal, Gerard Waeber, Peter Vollenweider, Armin von Gunten, Martin Preisig, Christine Kuehner, Enrique Castelao, Raphaël Heinzer, Julius Popp Tags: Negative results Source Type: research

Clinical features and genetic characterization of two dizygotic twins with intermediate C9orf72 expansion
To present a detailed clinical, genetic, and epigenetic characterization of two ALS concordant dizygotic (DZ) twins. The described cases underwent clinical and paraclinical examinations according to the motor neuron disease protocol of our referral center. Mutation analysis of the major causative genes related to ALS was performed. The methylation profile of the CpG-island located in the promoter region of C9orf72 and in the repeat region itself was investigated by bisulfite sequencing of C9orf72 expansion carriers. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 10, 2018 Category: Neuroscience Authors: F.L. Conforti, R. Tortelli, G. Morello, R. Capozzo, M.R. Barulli, S. Cavallaro, G. Logroscino Source Type: research

Levels of retinal IAPP are altered in Alzheimer ´s disease patients and correlate with vascular changes and hippocampal IAPP levels
Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer ’s disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD and non-demented controls (NC) were analysed using ELISA. Number of pericytes and vessel length were determined b y analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fraction contained increased levels of the same. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 10, 2018 Category: Neuroscience Authors: Nina Schultz, Elin Byman, the Netherlands Brain Bank, Malin Wennstr öm Source Type: research

Genetic screening in early-onset dementia patients with unclear phenotype: relevance for clinical diagnosis
In a prospective study of dementia in Flanders-Belgium, we observed a substantial fraction of early-onset dementia patients who did not fulfill the criteria for a specific dementia subtype, leaving the patients without a precise clinical diagnosis. We selected 211 of these patients for genetic testing of causal genes linked to neurodegenerative brain diseases. In this group, the onset or inclusion age was 59.9 ± 8.2 years and 27% had a positive family history. We used a panel of 16 major genes linked to Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson’s disease and p...
Source: Neurobiology of Aging - May 9, 2018 Category: Neuroscience Authors: Federica Perrone, Rita Cacace, Sara Van Mossevelde, Tobi Van den Bossche, Peter P. De Deyn, Patrick Cras, Sebastiaan Engelborghs, Julie van der Zee, Christine Van Broeckhoven Source Type: research

Stable olfactory sensory neuron in vivo physiology during normal aging
Normal aging is associated with a number of smell impairments that are paralleled by age-dependent changes in the peripheral olfactory system, including decreases in olfactory sensory neurons (OSNs) and in the regenerative capacity of the epithelium. Thus, an age-dependent degradation of sensory input to the brain is one proposed mechanism for the loss of olfactory function in older populations. Here, we tested this hypothesis by performing in vivo optical neurophysiology in 6, 12, 18, and 24 month-old mice. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 8, 2018 Category: Neuroscience Authors: Marley D. Kass, Lindsey A. Czarnecki, John P. McGann Tags: Negative results Source Type: research

Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients
Intermediate-length CAG repeat expansions in the ATXN2 gene (which encodes for the protein Ataxin-2) have been linked to increased risk for Amyotrophic Lateral Sclerosis (ALS) in different populations. There is no such study in the Brazilian population, which has a mixed ethnic background. We have thus selected 459 patients with ALS (372 Sporadic ALS and 87 Familial ALS) and 468 control subjects from 6 Brazilian centers to investigate this point. We performed polymerase chain reaction (PCR) to determine the length of the ATXN2 alleles. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 8, 2018 Category: Neuroscience Authors: Helen Maia Tavares de Andrade, V ívian Pedigone Cintra, Milena de Albuquerque, Camila Callegari Piccinin, Luciana Cardoso Bonadia, Rafael Esteves Duarte Couteiro, Daniel Sabino de Oliveira, Rinaldo Claudino, Marcos Vinicius Magno Gonçalves, Mario Emilio Tags: Brief communication Source Type: research

Telomere Attrition is Associated with Declines in Medial Temporal Lobe Volume and White Matter Microstructure in Functionally-Independent Older Adults
Although leukocyte telomere length (TL) shortens over the lifespan and is associated with diseases of aging, little is known about the relationships between TL, memory, and brain structure. 69 functionally-normal older adults (mean age=71.7) were assessed at two time points (mean interval=2.9years). Linear mixed models assessed relationships between TL and hippocampal volume, fractional anisotropy (FA) and mean diffusivity (MD) of the fornix, and verbal and visual episodic memory. Unstandardized coefficients are reported below, and p values are not corrected for multiple comparisons. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 8, 2018 Category: Neuroscience Authors: Adam M. Staffaroni, Duygu Tosun, Jue Lin, Fanny M. Elahi, Kaitlin B. Casaletto, Matthew J. Wynn, Nihar Patel, John Neuhaus, Samantha M. Walters, Elissa S. Epel, Elizabeth H. Blackburn, Joel H. Kramer Source Type: research

Phosphorylation of SET mediates apoptosis via P53 hyperactivation and NM23-H1 nuclear import
Apoptosis plays an important role in neuron loss in Alzheimer ’s disease (AD). SET, an endogenous inhibitor of protein phosphatase-2A (PP2A), is phosphorylated in AD brains and positively correlates with cell apoptosis. However, the mechanism underlying phosphorylated SET association with apoptosis remains unknown. Here we show that mimetic phosphorylation o f SET (S9E) induced apoptosis of primary cultured neurons. To investigate its mechanism, we overexpressed SET (S9E) in HEK 293/tau cells and observed apoptosis accompanied with a marked increase of cleaved caspase-3 and cytoplasmic SET (S9E) retention with enhanc...
Source: Neurobiology of Aging - May 8, 2018 Category: Neuroscience Authors: Mengjuan Wu, Guang Yu, Tonghai Yan, Dan Ke, Qun Wang, Rong Liu, Jian-Zhi Wang, Bin Zhang, Dan Chen, Xiaochuan Wang Source Type: research

FTDP-17 mutations enhance tau oligomer formation
The P301L mutation in tau, a microtubule-associated protein, causes frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17) that is accompanied by formation of filamentous polymers of tau. The mutation reduces the binding capability of microtubules and enhances tau filament formation. However, it is unclear whether the P301L mutation increases the formation of the intermediates of tau filaments, which are suggested to be a toxic species of tau. To determine the amount and structure of the intermediates harboring with the P301L mutation, we purified recombinant versions of wild-type, P301L, and four othe...
Source: Neurobiology of Aging - May 7, 2018 Category: Neuroscience Authors: Sumihiro Maeda, Yuhei Sato, Akihiko Takashima Source Type: research

The total number of myelinated nerve fibers is reduced in corpus callosum in brains from patients with Alzheimer ´s disease
We have estimated the total number of myelinated fibers in corpus callosum (CC) from brains of Alzheimer patients and control subjects using a two-dimensional fractionator principle. The total number of fibers in ten females Alzheimer patients (AD) (mean age 82.8 years) and twelve female control subjects (mean age 80.6 years) showed the mean number of myelinated fibers was significantly 30% higher in the control group (90.0x106; coefficient of variation (CV)=SD/mean=27%) than in the AD group (69.3x106; CV=20%) (p=0.028). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 7, 2018 Category: Neuroscience Authors: Nicolai K øster Rimvall, Jesper Riise, Bente Pakkenberg Source Type: research

Lifestyle-dependent Brain Change: A Longitudinal Cohort MRI Study
We investigated both independent and interconnected effects of three lifestyle factors on brain volume, measuring yearly changes using large-scale longitudinal magnetic resonance imaging, in middle-aged to older adults. We measured brain volumes in a cohort (n = 984, 49 –79 years) from the Korean Genome and Epidemiology Study group, using baseline and follow-up estimates after four years. In our analysis, the accelerated brain atrophy in normal aging was observed across regions (e.g., brain tissue: -0.098 ± 0.01 mL/year, p (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 7, 2018 Category: Neuroscience Authors: Regina EY. Kim, Chang-Ho Yun, Robert J. Thomas, Jang-Hoon Oh, Hans J. Johnson, Soriul Kim, Seungku Lee, Hyung Suk Seo, Chol Shin Source Type: research

Epistatic interaction of APOE and LSR genetic variants is associated with Alzheimer ’s disease
This study aimed to determine the potential interactions between two LSR genetic variants, rs34259399 and rs916147 and the APOE common polymorphism in 142 AD subjects (mean age: 73.16 ± 8.50 years) and 63 controls (mean age: 70.41 ± 8.49 years). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 3, 2018 Category: Neuroscience Authors: T. Xie, S. Akbar, M.G. Stathopoulou, T. Oster, C. Masson, F.T. Yen, S. Visvikis-Siest Source Type: research

DNAJC12 mutation is rare in Chinese Han population with Parkinson's disease
This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson's disease (PD) and test whether an age-of-onset effect exists. Seven hundred two Chinese Han sporadic PD patients, including 181 early-onset PD and 521 late-onset PD, and 728 healthy controls were recruited. No documented disease-causing mutation of DNAJC12 was identified, but we found 7 single-nucleotide polymorphisms. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 2, 2018 Category: Neuroscience Authors: Yu Fan, Zhi-hua Yang, Fang Li, Xin-chao Hu, Yi-wei Yue, Jing Yang, Yu-tao Liu, Han Liu, Yan-lin Wang, Chang-he Shi, Yu-ming Xu Tags: Genetic reports abstract Source Type: research

DNAJC12 mutation is rare in Chinese Han population with Parkinson ’s disease
This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson ’s disease (PD) and test whether an age-of-onset effect exists. 702 Chinese Han sporadic PD patients, including181 Early-onset Parkinson’s disease (EOPD) and 521 Late-onset Parkinson’s disease (LOPD), and 728 healthy controls were recruited. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 2, 2018 Category: Neuroscience Authors: Yu Fan, Zhi-hua Yang, Fang Li, Xin-chao Hu, Yi-wei Yue, Jing Yang, Yu-tao Liu, Han Liu, Yan-lin Wang, Chang-he Shi, Yu-ming Xu Tags: Negative results Source Type: research

Reduction of the molecular chaperone BiP accentuates the effect of aging on sleep-wake behavior
Sleep and wake quality, quantity and architecture become modified with aging. Sleep and wake quality decline coinciding with increased fragmentation of both states across aging. We have previously shown that this age-related decline in sleep-wake quality is associated with increased endoplasmic reticular (ER) stress and decreased expression of the major ER chaperone BiP (Binding immunoglobulin Protein). BiP, also known as glucose-regulated protein 78 (GRP78), plays a key role in controlling the cellular response to ER stress, acting as a regulator of a protein homeostatic signaling pathway known as the unfolded protein res...
Source: Neurobiology of Aging - April 30, 2018 Category: Neuroscience Authors: Nirinjini Naidoo, Jingxu Zhu, Raymond J. Galante, Jie Lian, Ewa Strus, Amy Lee, Brendan T. Keenan, Allan I. Pack Source Type: research

Cover 2: Editorial Advisory Board
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 26, 2018 Category: Neuroscience Source Type: research

Contents Continued
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 26, 2018 Category: Neuroscience Source Type: research

Cover 4: Contents
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 26, 2018 Category: Neuroscience Source Type: research

Cover 2: Editorial Advisory Board
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 25, 2018 Category: Neuroscience Source Type: research

Contents Continued
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Source: Neurobiology of Aging - April 25, 2018 Category: Neuroscience Source Type: research

Cover 4: Contents
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 25, 2018 Category: Neuroscience Source Type: research

Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework
A long-standing question is how to best use brain morphometric and genetic data to distinguish Alzheimer's disease (AD) patients from cognitively normal (CN) subjects and to predict those who will progress from mild cognitive impairment (MCI) to AD. Here, we use a neural network (NN) framework on both magnetic resonance imaging-derived quantitative structural brain measures and genetic data to address this question. We tested the effectiveness of NN models in classifying and predicting AD. We further performed a novel analysis of the NN model to gain insight into the most predictive imaging and genetics features and to ide...
Source: Neurobiology of Aging - April 24, 2018 Category: Neuroscience Authors: Kaida Ning, Bo Chen, Fengzhu Sun, Zachary Hobel, Lu Zhao, Will Matloff, Alzheimer's Disease Neuroimaging Initiative, Arthur W. Toga Source Type: research

Classifying Alzheimer ’s disease with brain imaging and genetic data using a neural network framework
A long-standing question is how to best use brain morphometric and genetic data to distinguish AD patients from cognitively normal (CN) subjects and to predict those who will progress from mild cognitive impairment (MCI) to AD. Here we use a neural network (NN) framework on both magnetic resonance imaging-derived quantitative structural brain measures and genetic data to address this question. We tested the effectiveness of NN models in classifying and predicting AD. We further performed a novel analysis of the NN model to gain insight into the most predictive imaging and genetics features, and to identify possible interac...
Source: Neurobiology of Aging - April 24, 2018 Category: Neuroscience Authors: Kaida Ning, Bo Chen, Fengzhu Sun, Zachary Hobel, Lu Zhao, Will Matloff, Alzheimer ’s Disease Neuroimaging Initiative, Arthur W. Toga Source Type: research

Mutation Screening of the TIA1 Gene in Chinese Patients with Amyotrophic Lateral Sclerosis/Frontotemporal Dementia
Mutations in the low complexity domain (LCD) of T-cell intracellular antigen-1 (TIA1) have been reported to be associated with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) in the Caucasian population. In the current study, we aimed to screen mutations in the LCD (exon 11-13) of TIA1 and determine the mutation frequency in Chinese ALS/FTD patients. A total of 740 ALS patients, including 721 sporadic ALS (sALS), 19 familial ALS (fALS), 24 FTD patients and 501 healthy controls (HCs), were directly sequenced. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 24, 2018 Category: Neuroscience Authors: XiaoJing Gu, YongPing Chen, QianQian Wei, Bei Cao, RuWei Ou, XiaoQin Yuan, YanBin Hou, LingYu Zhang, Hui Liu, XuePing Chen, Hui-Fang Shang Tags: Brief communication Source Type: research

Classifying Alzheimer ’s disease with brain imaging and genetic data using a neural network framework
A long-standing question is how to best use brain morphometric and genetic data to distinguish AD patients from cognitively normal (CN) subjects and to predict those who will progress from mild cognitive impairment (MCI) to AD. Here we use a neural network (NN) framework on both magnetic resonance imaging-derived quantitative structural brain measures and genetic data to address this question. We tested the effectiveness of NN models in classifying and predicting AD. We further performed a novel analysis of the NN model to gain insight into the most predictive imaging and genetics features, and to identify possible interac...
Source: Neurobiology of Aging - April 24, 2018 Category: Neuroscience Authors: Kaida Ning, Bo Chen, Fengzhu Sun, Zachary Hobel, Lu Zhao, Will Matloff, Alzheimer ’s Disease Neuroimaging Initiative, Arthur W. Toga Source Type: research

Mutation Screening of the TIA1 Gene in Chinese Patients with Amyotrophic Lateral Sclerosis/Frontotemporal Dementia
Mutations in the low complexity domain (LCD) of T-cell intracellular antigen-1 (TIA1) have been reported to be associated with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) in the Caucasian population. In the current study, we aimed to screen mutations in the LCD (exon 11-13) of TIA1 and determine the mutation frequency in Chinese ALS/FTD patients. A total of 740 ALS patients, including 721 sporadic ALS (sALS), 19 familial ALS (fALS), 24 FTD patients and 501 healthy controls (HCs), were directly sequenced. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 24, 2018 Category: Neuroscience Authors: XiaoJing Gu, YongPing Chen, QianQian Wei, Bei Cao, RuWei Ou, XiaoQin Yuan, YanBin Hou, LingYu Zhang, Hui Liu, XuePing Chen, Hui-Fang Shang Tags: Brief communication Source Type: research

Age Affects Reinforcement Learning through Dopamine-based Learning Imbalance and High Decision Noise — not through Parkinsonian Mechanisms
Probabilistic reinforcement learning declines in healthy cognitive aging. While some findings suggest impairments are especially conspicuous in learning from rewards, resembling deficits in Parkinson ’s disease, others also show impairments in learning from punishments. To reconcile these findings, we tested 252 adults from three age groups on a probabilistic reinforcement learning task, analyzed trial-by-trial performance with a Q-reinforcement learning model, and correlated both fitted model parameters and behavior to polymorphisms in dopamine-related genes. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 18, 2018 Category: Neuroscience Authors: Ravi B. Sojitra, Itamar Lerner, Jessica. R. Petok, Mark A. Gluck Source Type: research

Sexual dimorphism in predisposition to Alzheimer's disease
Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and rate of symptom progression, but the mechanisms underlying this sexual divergence are unknown. Although some have suggested this difference in risk is a reflection of the known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities toward the disease. Although a number of potential risk factors have been hypothesized to mediate these differences, none have been definitively verified. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - April 17, 2018 Category: Neuroscience Authors: Daniel W. Fisher, David A. Bennett, Hongxin Dong Tags: Review Source Type: research