Endosomal dysfunction impacts extracellular vesicle release: central role in A β pathology.

Endosomal dysfunction impacts extracellular vesicle release: central role in Aβ pathology. Ageing Res Rev. 2019 Dec 28;:101006 Authors: Arbo BD, Cechinel LR, Palazzo RP, Siqueira IR Abstract Alzheimer's Disease (AD) is characterized by progressive loss of cognitive abilities; senile plaques represent the major histopathological findings. Amyloid precursor protein (APP) processing machinery, and its product amyloid-beta (Aβ) peptide, have been found in extracellular vesicles (EVs), specifically exosomes, which allows for Aβ peptide aggregation and subsequent senile plaques deposition. We review the APP processing imbalance in EVs, autophagic and endosomal pathways in AD. Increased intraluminal vesicle (ILV) production and exosome release appear to counteract the endosomal dysfunction of APP processing; however, this process results in elevated amyloidogenic processing of APP and augmented senile plaque deposition. Several players related to APP processing and dysfunctional endosomal-lysosomal-exosomal (and other EVs) pathway are described, and the interconnected systems are discussed. The components Arc, p75, Rab11 and retromer complex emerge as candidates for key convergent mechanisms that lead to increased EVs loaded with APP machinery and Aβ levels, in atrophy and damage of basal forebrain cholinergic neurons in AD. PMID: 31891813 [PubMed - as supplied by publisher]
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research

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Analyst, 2020, Accepted Manuscript DOI: 10.1039/D0AN00924E, PaperYong-Ill Lee, Qi Ou, Salah Mahmoud Tawfik, xinfeng Zhang An increasing number of patients are living with Alzheimer's disease (AD); thus, the need for a method to detect AD early and sensitively has become urgent, and the demand for... The content of this RSS Feed (c) The Royal Society of Chemistry
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Conditions:   Alzheimer Disease;   Dementia Interventions:   Device: tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS.;   Device: tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver sham tDCS. Sponsors:   Albert Einstein College of Medicine;   MJHS Institute for Innovation in Palliative Care Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
This study aimed to investigate the neural correlates of hippocampal downregulation associated with core Alzheimer's disease CSF biomarkers.Brain
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Neurology & Neurosurgery Journal Article Source Type: news
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Source: Medscape Today Headlines - Category: Consumer Health News Tags: Psychiatry News Source Type: news
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Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.0c00278
Source: Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research
In this study, our previously proposed persistent features and various traditional graph-theoretical measures are used to quantify the topological property of white matter (WM) network in 150 subjects with diffusion tensor imaging (DTI). We found significant differences in these measures among AD, MCI, and normal controls (NC) under different brain parcellation schemes. The decreased network integration and increased network segregation are presented in AD and MCI. Moreover, the persistent homology-based measures demonstrated stronger statistical capability and robustness than traditional graph-theoretic measures, suggesti...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Alzheimer's disease (AD) has an estimated prevalence of 50 million persons worldwide1 and an incidence of 10 million cases per year1-3, making it the most common form of dementia. While neuropsychiatric symptoms (NPS) are common in AD, apathy is particularly frequent, affecting up to 70% of patients4. Apathy has been broadly defined as a loss of interest in daily activities and diminished goal directed behavior in the absence of depression and other mood changes5 –7 . This NPS is associated with greater functional impairment, greater caregiver burden, increased risk of institutionalization, poorer quality of life, an...
Source: The American Journal of Geriatric Psychiatry - Category: Geriatrics Authors: Tags: Regular Research Article Source Type: research
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Source: Translational Neurodegeneration - Category: Neurology Source Type: research
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