ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022
APP accumulates with presynaptic proteins around amyloid plaques: A role for presynaptic mechanisms in Alzheimer's disease?
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Value of blood neural cell-derived small extracellular vesicles in the diagnosis and prediction of Alzheimer's disease: A systematic review.The journal of prevention of Alzheimer's disease · 2025Pooled it
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
- Aberrant ɑSMA expression reveals broad mossy fiber reorganization integrating with tangle and plaque formation and mitoenergetic alteration in the human hippocampus.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
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- Presenilin-1 Affects Melanoma Cell Behavior in an Amyloid Precursor Protein-Rich, Alzheimer's Disease-like, Microenvironment.International journal of molecular sciences · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.bioRxiv : the preprint server for biology · 2026Article
- 3,4-Dihydroxybenzaldehyde Exerts Anti-Alzheimer's Effects by Inhibiting Aβ Protofibril Assembly and Activating Antioxidant Defense Mechanisms.International journal of molecular sciences · 2026Article
- Systematic post-translational modification genome wide identifies therapeutic targets for Alzheimer's disease: evidence from multi-cohort analysis.The journal of prevention of Alzheimer's disease · 2026Article
- Lysosomal protease-mediated APP degradation is pH-dependent, mutation-sensitive, and facilitates tau proteolysis.Molecular neurodegeneration advances · 2026Article
- Detergent-free isolation and characterization of amyloid precursor protein C99 in E. coli native lipid-nanodiscs using non-ionic polymer.Protein science : a publication of the Protein Society · 2025Article
- Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The amyloid precursor family of proteins in excitatory neurons are essential for regulating cortico-hippocampal circuit dynamics in vivo.Cell reports · 2025Article
- Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease.Immunity · 2025Article
- Annexin A6 membrane repair protein protects against amyloid-induced dystrophic neurites and tau phosphorylation in Alzheimer's disease model mice.Acta neuropathologica · 2025Article
- Astrocytic Hevin/SPARCL-1 Regulates Cognitive Decline in Pathological and Normal Brain Aging.Aging cell · 2025Article
- Article
- Transmembrane and coiled-coil 2 associates with Alzheimer's disease pathology in the human brain.Brain pathology (Zurich, Switzerland) · 2025Article
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- Altered ubiquitin signaling induces Alzheimer's disease-like hallmarks in a three-dimensional human neural cell culture model.Nature communications · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Alzheimer's disease (AD), the distribution of the amyloid precursor protein (APP) and its fragments other than amyloid beta, has not been fully characterized. Here, we investigate the distribution of APP and its fragments in human AD brain samples and in mouse models of AD in reference to its proteases, synaptic proteins, and histopathological features characteristic of the AD brain, by combining an extensive set of histological and analytical tools. We report that the prominent somatic distribution of APP observed in control patients remarkably vanishes in human AD patients to the benefit of dense accumulations of extra-somatic APP, which surround dense-core amyloid plaques enriched in APP-Nter. These features are accentuated in patients with familial forms of the disease. Importantly, APP accumulations are enriched in phosphorylated tau and presynaptic proteins whereas they are depleted of post-synaptic proteins suggesting that the extra-somatic accumulations of APP are of presynaptic origin. Ultrastructural analyses unveil that APP concentrates in autophagosomes and in multivesicular bodies together with presynaptic vesicle proteins. Altogether, alteration of APP distribution and its accumulation together with presynaptic proteins around dense-core amyloid plaques is a key histopathological feature in AD, lending support to the notion that presynaptic failure is a strong physiopathological component of AD.
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