Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
Year: 2019
Type: review
Abstract: Increasing evidence supports that cellular dysregulations in the degradative routes contribute to the initiation and progression of neurodegenerative diseases, including Alzheimer's disease. Autophagy and endolysosomal homeostasis need to be maintained throughout life as they are major cellular mechanisms involved in both the production of toxic amyloid peptides and the clearance of misfolded or aggregated proteins. As such, alterations in endolysosomal and autophagic flux, as a measure of degradation activity in these routes or compartments, may directly impact as well on disease-related mechanisms such as amyloid-β clearance through the blood-brain-barrier and the interneuronal spreading of amyloid-β and/or Tau seeds, affecting synaptic function, plasticity and metabolism. The emerging of several genetic risk factors for late-onset Alzheimer's disease that are functionally related to endocytic transport regulation, including cholesterol metabolism and clearance, supports the notion that in particular the autophagy/lysosomal flux might become more vulnerable during ageing thereby contributing to disease onset. In this review we discuss our current knowledge of the risk genes APOE4, BIN1, CD2AP, PICALM, PLD3 and TREM2 and their impact on endolysosomal (dys)regulations in the light of late-onset Alzheimer's disease pathology.
Source: Molecular Neurodegeneration
Authors: Zoë P. Van Acker, Marine Bretou, Wim Annaert
Institutions: VIB-KU Leuven Center for Brain & Disease Research, KU Leuven
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,580
Awards: Bridging microscopy with nanotechnology and interactomics to probe the membrane microenvironment of distinct y-secretase complexes in cells and neurons and to identify complex-specific interactors, Role y-secretase heterogeneity in intracellular AB production, lysosomal toxicity, and pathogenesis: contribution of familial Alzheimer’s disease mutations in presenilins and late onset Alzheimer’s disease risk factors, Integrated platform to validate vesicular trafficking-associated processes in neurodegenerative diseases., Infrastructure enabling correlative light and electron microscopy for the Life Sciences., New neuronal models for intracellular toxic Aß accumulation, G7198459672, G7988088860, G8430873857
OpenAlex ID: W2948656839