Amyloid, the presenilins and Alzheimer’s disease

Hardy, J

doi:10.1016/s0166-2236(96)01030-2

Cited by 1,370Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid, the presenilins and Alzheimer’s disease

Hardy, J·1997·Trends in Neurosciences

DOI 10.1016/s0166-2236(96)01030-2

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Abstract

Various mutations in the amyloid protein precursor and presenilin genes can lead to early onset, autosomal Alzheimer's disease. A series of mis-sense mutations (with one exception) in each of these genes has been shown to cause disease in a fully penetrant fashion. It has recently been shown, both in vivo and in model systems, that tissues expressing these mutations have increased production of amyloid (A beta) ending at residue 42. It has also recently been shown that this form of A beta is deposited early and selectively in the disease process and is more fibrillogenic in vitro. It is argued that these genetic and molecular biological data provide strong support for the veracity of the 'amyloid cascade hypothesis' for disease pathogenesis, and that this hypothesis offers a coherent framework for drug discovery.

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Individuals who inherited the APOEε4 allele from an African ancestor had a lower risk of developing Alzheimer's disease than an individual who inherited APOEε4 from a European ancestor.
“individuals that inherited the APOEε4 allele (and surrounding region) from an African ancestor had a lower risk of developing AD than an individual who inherited APOEε4 from a European ancestor [62, 102].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [102]
Total Aβ burden depends on the balance between production and clearance or degradation rates.
“The total Aβ burden depends on the balance between production and clearance or degradation rates (Hardy, 1997; George-Hyslop and Rossor, 2001).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Hardy, 1997

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Authors: Hardy, J.
Affiliations: Mayo Clinic in Florida (US)
Corresponding author: Hardy, J
ORCID: Hardy, J
Venue: Trends in Neurosciences
Publisher: Elsevier BV
Published: 1997-05-13
Volume: 20
Issue: 4
Pages: 154-159
ISSN: 0166-2236 (ISSN-L)
DOI: 10.1016/s0166-2236(96)01030-2
OpenAlex: W2029205666
Cited by: 1,370
References: 34
Citations by year: 2026: 7 · 2025: 10 · 2024: 15 · 2023: 14 · 2022: 20 · 2021: 19 · 2020: 22 · 2019: 14 · 2018: 25 · 2017: 21 · 2016: 30 · 2015: 27 · 2014: 37 · 2013: 37 · 2012: 48
FWCI: 73.04
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Neurosciences (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
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 › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, amyloid precursor protein, presenilin, early-onset familial Alzheimer's disease, missense mutations, amyloid-beta 42, amyloid hypothesis, pathogenesis, drug discovery
MeSH terms: Alzheimer Disease, Humans, Membrane Proteins, Amyloid beta-Peptides, Presenilin-1

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Amyloid, the presenilins and Alzheimer’s disease

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