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Is amyloid-β harmful to the brain? Insights from human imaging studies

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Jagust, William·2016·Brain
DOI 10.1093/brain/awv326PMC PMC4990654
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Abstract

Although the amyloid-β protein associated with the Alzheimer’s disease plaque has been detectable in living people for over a decade, its importance in the pathogenesis of Alzheimer’s disease is still debated. The frequent presence of amyloid-β in the brains of cognitively healthy older people has been interpreted as evidence against a causative role. If amyloid-β is crucial to the development of Alzheimer’s disease, it should be associated with other Alzheimer’s disease-like neurological changes. This review examines whether amyloid-β is associated with other biomarkers indicative of early Alzheimer’s disease in normal older people. The preponderance of evidence links amyloid-β to functional change, progressive brain atrophy, and cognitive decline. Individuals at greatest risk of decline seem to be those with evidence of both amyloid-β and findings suggestive of neurodegeneration. The crucial question is thus how amyloid-β is related to brain degeneration and how these two processes interact to cause cognitive decline and dementia. The presence of β-amyloid in the brain may represent a preclinical stage of Alzheimer’s disease, but this is controversial. Jagust examines the association between β-amyloid and biomarkers of Alzheimer’s disease in cognitively normal older people, concluding that β-amyloid is harmful to the brain in a manner consistent with Alzheimer’s disease.

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  • Many older individuals have considerable Aβ in the brain, yet do not display cognitive deficits or dementia when compared to age-matched controls without Aβ accumulation.

    “Many older individuals have considerable Aβ in the brain, yet do not display cognitive deficits or dementia when compared to age-matched controls without Aβ accumulation [107,108].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [107]

    The Introduction (p. 2) and the section on cognition in normal older people (p. 4) discuss older people with brain amyloid-β who remain cognitively normal; the latter notes that some cross-sectional studies found no cognitive association. But the same section reports subtle deficits in other studies, a small association with episodic memory in a meta-analysis, and greater subsequent decline in people with amyloid-β than in those without. The claim overstates the absence of cognitive differences compared with amyloid-negative peers. (LLM, conf=0.85)

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Authors
Jagust, W.
Affiliations
University of California, Berkeley (US)
Corresponding author
Jagust, William
ORCID
Jagust, William
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2015-11-27
Volume
139
Issue
1
Pages
23-30
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awv326
PMC
PMC4990654
OpenAlex
W2177509216
Cited by
110
References
16
Citations by year
2026: 6 · 2025: 11 · 2024: 6 · 2023: 14 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 12 · 2018: 10 · 2017: 15 · 2016: 9
FWCI
1.56
Type
journal article
Language
en
Open access
Locations
  • Brain (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (AG034570)
  • National Institute on Aging (AG034570, R01AG034570)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
amyloid-beta, Alzheimer's disease, preclinical Alzheimer's disease, brain atrophy, cognitive decline, neurodegeneration, amyloid plaques, neuroimaging biomarkers, older adults, dementia
MeSH terms
Alzheimer Disease, Brain, Cognition Disorders, Humans, Nerve Degeneration, Biomarkers, Amyloid beta-Peptides, Positron-Emission Tomography, Functional Neuroimaging

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