ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Blood gene expression network expression strongly relates to brain amyloid burden.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Whole blood gene expression moderates associations between AD biomarkers and cognitive decline in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Blood gene expression network expression strongly relates to brain amyloid burden.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Authors and funding
10 authors.
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Abstract
introductionAmyloid deposition occurs decades before symptoms emerge in Alzheimer's disease (AD). We leveraged blood transcriptomics and positron emission tomography (PET) measures of amyloidosis to identify gene networks in the blood that relate to amyloid burden in the brain.
methodsWhole-blood RNA sequencing and amyloid PET were leveraged from 1739 cognitively unimpaired participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. Linear regression related gene module expression to amyloid covarying for age, sex, education, and apolipoprotein E (APOE) ε2 and ε4 genotypes.
resultsOf the 18 gene modules, one histone gene cluster module was associated with amyloid (β = -0.55, false discovery rate-adjusted p value = 0.029). We also observed nominal associations for the predicted proportion of activated natural killer (NK) cells (β = -0.454, p = 0.02) and CD4+ activated memory T cells (β = -0.169, p = 0.03) with amyloid deposition. DISCUSSION: Our results implicate the histone gene cluster on chromosome 6 and immune cell proportions as blood correlates of brain amyloid deposition in preclinical AD. HIGHLIGHTS: Higher expression of network module with histone gene cluster on chromosome 6 associated with lower amyloid levels. Four histone genes, H1-5, H3C3, H2BC3, H2AC14, and RRM2, emerged as key genes driving this association, where H1-5 emerged as a hub gene for this module. Pathways, including nucleosome assembly and DNA damage, were enriched in the histone module. A higher fraction of activated NK and activated CD4+ T cells was related to lower amyloid burden.
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