Discrete pools of oligomeric amyloid- β track with spatial learning deficits in a mouse model of Alzheimer amyloidosis.

Discrete pools of oligomeric amyloid-β track with spatial learning deficits in a mouse model of Alzheimer amyloidosis. Am J Pathol. 2017 Dec 14;: Authors: Chiang ACA, Fowler SW, Reddy R, Pletnikova O, Troncoso JC, Sherman MA, Lesne SE, Jankowsky JL Abstract Despite increasing appreciation that oligomeric amyeloid beta (Aβ) may contribute to cognitive decline of Alzheimer disease, defining the most critical forms has been thwarted by the changeable nature of these aggregates and the varying methods used for detection. Here, using a broad approach, we quantified Aβ oligomers during the evolution of cognitive deficits in an aggressive model of Aβ amyloidosis. Amyloid precursor protein/tetracycline transactivator mice underwent behavioral testing at 3, 6, 9, and 12 months of age to evaluate spatial learning and memory, followed by histological assessment of amyloid burden and biochemical characterization of oligomeric Aβ species. Transgenic mice displayed progressive impairments in acquisition and immediate recall of the trained platform location. Biochemical analysis of cortical extracts from behaviorally tested mice revealed distinct age-dependent patterns of accumulation in mulitple oligomeric species. Dot blot analysis demonstrated that non-fibrillar Aβ oligomers (A11) were highly soluble and extracted into a fraction enriched for extracellular proteins, whereas pre-fibrillar (OC) species required high-detegerent conditions ...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research

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This study was carried out in accordance with the recommendations of the National Animal Care and Use Committee of the University of Buenos Aires (CICUAL). The protocol was approved by the CICUAL. Mice were kept under a 12-h light/dark cycle, with controlled temperature (23 ± 2°C) and humidity (40–60%) and had ad libitum access to food and water. To produce hTDP-43 transgenic lines, as described previously (Igaz et al., 2011), pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings were injected with a vector containing hTDP-43-WT cDNA. Monogenic tetO-TDP-WT12 mice wer...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study, a link between mitochondrial changes and infant temperament has also been suggested. Maternal psychosocial stress and lifetime trauma have been associated with decreased mitochondrial DNA copy number in the placenta (115, 116).IndividualityChronic stress links changes in the epigenetic landscape with health conditions (117). Different cell types are characterized by distinct patterns of gene expression due to developmental, environmental, physiological, and pathological reasons (117). Epigenetic mechanisms affect gene function in a dynamic way as a result of different environmental exposures during fetal dev...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Publication date: Available online 16 April 2019Source: NeuroscienceAuthor(s): Kimberley E. Stuart, Anna E. King, Natalie E. King, Jessica M. Collins, James C. Vickers, Jenna M. ZiebellAbstractEnvironmental enrichment (EE) has been consistently reported to enhance cognitive function in mouse models of neuropathology. Microglia, implicated in Alzheimer's disease pathology, may mediate this effect. The aim of the present study was to investigate the effect of EE on cognitive function and microglia in mouse models of ageing and amyloidosis. Male wild-type (Wt) and APP/PS1 mice were randomly assigned to standard housing (SH) o...
Source: Neuroscience - Category: Neuroscience Source Type: research
Publication date: August 2019Source: Materials Science and Engineering: C, Volume 101Author(s): Agnishwar Girigoswami, M. Ramalakshmi, Najim Akhtar, Sanjay Kisan Metkar, Koyeli GirigoswamiAbstractAn electrokinetic potential (ζ-potential) based approach was introduced to address the amyloid degradation on ZnO-nanoflower platform. The hallmark of neurodegenerative disorders like Alzheimer's disease, Parkinson's disease (PD), Creutzfeldt-Jakob Disease (CJD), Prion- associated diseases, type-II diabetes, etc. is the deposition of misfolded protein aggregates predominantly β-sheeted in structure and fibrillar morpholo...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
Conclusion: This first PET investigation with longitudinal TSPO and amyloid PET together with terminal cognitive testing in an AD mouse model indicates that continuing microglial response seems to impart preserved cognitive performance.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Source Type: research
In conclusion, long-term aerobic exercise appears to attenuate the decline in endothelial vascular function, a benefit which is maintained during chronological aging. However, currently there is not enough evidence to suggest that exercise interventions improve vascular function in previously sedentary healthy older adults. Hijacking the Proteasome to Dispose of Unwanted Molecules in Age-Related Disease https://www.fightaging.org/archives/2019/03/hijacking-the-proteasome-to-dispose-of-unwanted-molecules-in-age-related-disease/ Cells are equipped with a protein disposal system in the form of the proteaso...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Alzheimer's disease (AD) is pathologically characterized by the deposition of the β-amyloid (Aβ) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the bridging integrator 1 (BIN1) gene within the second most significant susceptibility locus for late-onset AD. BIN1 is a member of the amphiphysin family of proteins and has reported roles in the generation of membrane curvature and endocytosis. Endocytic dysfunction is a pathological feature of AD, and endocytosis of the amyloid precursor protein is an i...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Molecular Bases of Disease Source Type: research
Therapeutic strategies targeting amyloid-β in Alzheimer's disease. Curr Alzheimer Res. 2019 Mar 21;: Authors: Pinheiroa L, Faustino C Abstract Alzheimer's disease (AD) is a neurodegenerative disorder linked to protein misfolding and aggregation. AD is pathologically characterized by senile plaques formed by extracellular amyloid-β (Aβ) peptide and intracellular neurofibrillary tangles (NFT) formed by hyperphosphorylated tau protein. Extensive synaptic loss and neuronal degeneration are responsible for memory impairment, cognitive decline and behavioral dysfunctions typical of AD. Amyloi...
Source: Current Alzheimer Research - Category: Neurology Authors: Tags: Curr Alzheimer Res Source Type: research
Publication date: Available online 13 March 2019Source: NeuroImage: ClinicalAuthor(s): Qing Wang, Yong Wang, Jingxia Liu, Courtney L. Sutphen, Carlos Cruchaga, Tyler Blazey, Brian A. Gordon, Yi Su, Charlie Chen, Joshua S. Shimony, Beau M. Ances, Nigel J. Cairns, Anne M. Fagan, John C. Morris, Tammie L.S. BenzingerAbstractInterest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer's disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion ...
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
AbstractThe amyloid cascade hypothesis dealing with the senile plaques is until date thought to be one of the causative pathways leading to the pathophysiology of Alzheimer ’s disease (AD). Though many aggregation inhibitors of misfolded amyloid beta (Aβ42) peptide have failed in clinical trials, there are some positive aspects of the designed therapeutic peptides for diseases involving proteinaceous aggregation. Here, we evaluated a smart design of side chain tripeptide (Leu-Val-Phe)-based polymeric inhibitor addressing the fundamental hydrophobic amino acid stretch “Lys-Leu-Val-Phe-Phe-Ala” (KLVFFA...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
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