Inflammation in the Alzheimer's disease cascade: culprit or innocent bystander?
Open accessAbstract
The strongest known risk factors for late-onset Alzheimer disease (LOAD) remain a positive family history and the APOE epsilon4 allele. van Exel and colleagues used these known risk factors to identify high- and low-risk samples of middle-aged persons in whom they compared levels of inflammatory and vascular risk factors. They observed that, compared with controls, middle-aged offspring of families with a parental history of LOAD had higher blood pressures, lower ankle-brachial indices (measure of peripheral atherosclerosis), and increased production of proinflammatory cytokines in lipopolysaccharide-stimulated whole blood samples, associations that were independent of APOE genotype. This study adds to the growing body of evidence linking inflammatory mechanisms to Alzheimer disease risk and, especially when considered in light of the recently described association of genetic variation in the complement receptor 1 (CR1) gene with LOAD, suggests that inflammatory biomarkers (whether causal or incidental) could be measured and perhaps used to risk-stratify middle-aged persons for early preventive and therapeutic interventions.
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Activated microglia may be involved in generation of Aβ plaque by increasing secretion of Aβ fragments; inducing IFITM3; or releasing iron which enhances aggregation of soluble β-amyloid.
“Activated microglia may be involved in the generation of Aβ plaque by increasing the secretion of Aβ fragments; inducing the expression of interferon-induced transmembrane protein 3 (IFITM3), a γ-secretase modulatory protein; or releasing agents such as iron, which enhances the aggregation of soluble β-amyloid.37–39”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [38]
The paper’s Abstract says cytokines may affect β-amyloid precursor-protein processing and that inflammation may amplify the amyloid cascade. It does not say activated microglia generate plaques by increasing Aβ-fragment secretion, inducing IFITM3, or releasing iron that promotes aggregation; the Abstract instead describes β-amyloid stimulating cytokine production by microglial cells. (LLM, conf=0.84)
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Cites
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- Authors
- Tan, Z. S., & Seshadri, S.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston University (US)
- Corresponding author
- Tan, Zaldy S
- Venue
- Alzheimer's Research & Therapy
- Published
- 2010
- Volume
- 2
- Issue
- 2
- Pages
- 6
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC2876784
- OpenAlex
- W2167673977
- Cited by
- 39
- References
- 5
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2017: 2 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (AG031287, N01-HC 25195, AG08122)
- National Institute on Aging (AG-16495, R01-AG-16495, N01-HC-25195, AG031287, AG08122, AG033193, P30AG013846, R01AG033193)
- National Institute of Neurological Disorders and Stroke (N01‐HC‐25195)
- 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, inflammation, late-onset Alzheimer's disease, APOE ε4, family history (medicine), vascular risk factors, blood pressure, ankle-brachial index, peripheral atherosclerosis, inflammatory cytokines, lipopolysaccharide stimulation, complement receptor 1, inflammatory markers, risk stratification, middle-aged adults
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