Endo‐lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?
Open accessAbstract
Alzheimer's disease (AD) is the most common cause of dementia, and its prevalence will increase significantly in the coming decades. Although important progress has been made, fundamental pathogenic mechanisms as well as most hereditary contributions to the sporadic form of the disease remain unknown. In this review, we examine the now substantial links between AD pathogenesis and lysosomal biology. The lysosome hydrolyses and processes cargo delivered by multiple pathways, including endocytosis and autophagy. The endo‐lysosomal and autophagic networks are central to clearance of cellular macromolecules, which is important given there is a deficit in clearance of amyloid‐β in AD. Numerous studies show prominent lysosomal dysfunction in AD, including perturbed trafficking of lysosomal enzymes and accumulation of the same substrates that accumulate in lysosomal storage disorders. Examination of the brain in lysosomal storage disorders shows the accumulation of amyloid precursor protein metabolites, which further links lysosomal dysfunction with AD. This and other evidence leads us to hypothesise that genetic variation in lysosomal genes modifies the disease course of sporadic AD. image
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Impairment of protein degradation pathways, including autophagy, is found in a host of neurodegenerative diseases.
“Impairment of protein degradation pathways, including autophagy (reviewed previously66–68), is found in a host of neurodegenerative diseases.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [66]
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- Authors
- Whyte, L. S., Lau, A. A., Hemsley, K. M., Hopwood, J. J., & Sargeant, T. J.
- Affiliations
- South Australian Health and Medical Research Institute (AU)
- Corresponding author
- Sargeant, Timothy J.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2017-01-23
- Volume
- 140
- Issue
- 5
- Pages
- 703-717
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2562785312
- Cited by
- 150
- References
- 172
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 14 · 2023: 10 · 2022: 20 · 2021: 24 · 2020: 16 · 2019: 18 · 2018: 21 · 2017: 4
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Rotary Health/Rotary Club of Adelaide
- Australian Postgraduate Award
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Alzheimer's disease, lysosomal dysfunction, autophagy, endolysosomal trafficking, amyloid-beta clearance, lysosomal storage disease, lysosomal enzyme trafficking, sporadic Alzheimer's disease, endocytosis
- MeSH terms
- Alzheimer Disease, Animals, Autophagy, Humans, Lysosomes, Lysosomal Storage Diseases, Nervous System
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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