The role of Aβ42 in Alzheimer's disease
Abstract
Our recent studies of plasma, fibroblasts, transfected cells and transgenic mice show that a fundamental effect of the mutations linked to familial Alzheimer's disease (FAD) is to increase the extracellular concentration of A beta 42. This effect of the FAD-linked mutations is likely to be directly related to the pathogenesis of Alzheimer's disease (AD) because A beta 42 is deposited early and selectively in the senile plaques that are an invariant feature of all forms of AD. Thus our results provide strong evidence that the FAD-linked mutations all cause AD by increasing the extracellular concentration of A beta 42 (43), thereby fostering A beta deposition, and they support the hypothesis that cerebral A beta deposition is an essential early event in the pathogenesis of all forms of AD. Interactions between the basal forebrain cholinergic system and A beta that could influence AD pathogenesis are discussed.
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A strong genetic association exists between early-onset familial Alzheimer's disease and the 42 amino acid species of Aβ peptide (Aβ42).
“A strong genetic association exists between earlyonset familial forms of AD (FAD) and the 42 amino acid species of the A 𝛃 peptide (A 𝛃 42 ) (for review, see Hutton et al., 1998; Younkin, 1998; Sisodia et al., 1999).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Younkin, 1998
Mutations in APP and presenilins PS1 and PS2 increase production of Aβ42 and cause familial Alzheimer's disease.
“Mutations in the genes for amyloid precursor protein (APP) and presenilins (PS1, PS2) increase production of 𝛃 -amyloid 42 (A 𝛃 42 ) and cause familial Alzheimer's disease (FAD).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Younkin, 1998
In vivo, Aβ42 is the predominant form of Aβ that accumulates in the AD brain and is essential for seeding Aβ deposition.
“In vivo, A42 is the predominant form of A that accumulates in the AD brain and is essential for seeding A deposition (Younkin, 1998;Fryer and Holtzman, 2005).”
From Aβ40 Inhibits Amyloid Deposition<i>In Vivo</i> (2007) · cites this paper as Younkin, 1998
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- Authors
- Younkin, S. G.
- Affiliations
- Mayo Clinic in Florida (US)
- Corresponding author
- Younkin, Steven G.
- Venue
- Journal of Physiology-Paris
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 92
- Issue
- 3-4
- Pages
- 289-292
- ISSN
- 0928-4257 (ISSN-L)
- OpenAlex
- W84124737
- Cited by
- 282
- References
- 10
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 12 · 2020: 10 · 2019: 13 · 2018: 7 · 2017: 9 · 2016: 12 · 2015: 12 · 2014: 12 · 2013: 11 · 2012: 17
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Physiology-Paris (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 › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta 42, Alzheimer's disease, familial Alzheimer's disease mutations, amyloid plaques, amyloid deposition, cholinergic system, Alzheimer's disease pathogenesis
- MeSH terms
- Alzheimer Disease, Animals, Clinical Trials as Topic, Humans, Mutation, Peptide Fragments, Amyloid beta-Peptides, Age of Onset
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