ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Network-dependent remote effects and local tau burden jointly shape neuronal dysfunction in Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTau pathology in Alzheimer's disease (AD) propagates along the brain's connectome, yet the mechanisms by which tau drives neuronal dysfunction remain unclear. We hypothesized that dysfunction primarily emerges in regions close to tau-harboring epicenters.
methodsOne hundred thirty-one amyloid-positive individuals underwent dynamic [
resultsAt the individual level, hypoperfusion was more closely related to distance from tau epicenters than to local tau deposition, particularly in early AD, consistent with diaschisis-like disconnection. With advancing biological disease severity, local tau deposition increasingly converged with hypoperfusion. Critically, hypoperfusion mediated the relationship between tau accumulation and cognitive decline. DISCUSSION: Tau epicenters shape the brain-wide pattern of neuronal dysfunction, while local tau burden determines the degree of damage driving cognitive decline.
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