Alzheimer's disease: The amyloid cascade hypothesis: An update and reappraisal
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Here I recap the scientific and personal background of the delineation of the amyloid cascade hypothesis for Alzheimer's disease that I wrote with Gerry Higgins and the events leading to the writing of that influential review.
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All high-penetrance AD genetic risk alleles (APOE ε4 allele, Down syndrome, APP mutations and duplications, PSEN1 and PSEN2 mutations) have been linked in various experimental systems with increased Aβ deposition and increased formation of putative toxic Aβ peptide species.
“All high-penetrance AD genetic risk alleles (i.e. APOE ε4 allele, Down syndrome, APP mutations and duplications, PSEN1 and PSEN2 mutations) have been linked in various experimental systems with increased Aβ deposition and increased formation of putative toxic Aβ peptide species (46, 55-57).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [55]
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- Authors
- Hardy, J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Hardy, John
- ORCID
- Hardy, John
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2006-07-27
- Volume
- 9
- Issue
- s3
- Pages
- 151-153
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1746907828
- Cited by
- 475
- References
- 13
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 21 · 2023: 22 · 2022: 17 · 2021: 29 · 2020: 35 · 2019: 30 · 2018: 34 · 2017: 28 · 2016: 22 · 2015: 31 · 2014: 25 · 2013: 29 · 2012: 25
- FWCI
- 14.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurology and Historical Studies
- Keywords
- Alzheimer's disease, amyloid hypothesis
- MeSH terms
- Alzheimer Disease, Brain, Humans, Amyloid beta-Peptides
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.
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