Inter-network functional connectivity increases by beta-amyloid and may facilitate the early stage of tau accumulation.

TitleInter-network functional connectivity increases by beta-amyloid and may facilitate the early stage of tau accumulation.
Publication TypeJournal Article
Year of Publication2025
AuthorsHojjati SHani, Butler TA, de Leon M, Gupta A, Nayak S, Luchsinger JA, Razlighi QR, Chiang GC
JournalNeurobiol Aging
Volume148
Pagination16-26
Date Published2025 Apr
ISSN1558-1497
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Female, Humans, Limbic System, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Positron-Emission Tomography, tau Proteins
Abstract

Alzheimer's disease (AD) is pathologically marked by tau tangles and beta-amyloid (Aβ) plaques. It has been hypothesized that Aβ facilitates spread of tau outside of the medial temporal lobe (MTL), but exact mechanism of this facilitation remains unclear. We aimed to test the hypothesis that abnormal Aβ induces an increase in inter-network functional connectivity, which in turn induces early-stage tau elevation in limbic network. Our study used 18F-Florbetaben Aβ positron emission tomography (PET), 18F-MK6240 tau-PET, and resting-state functional magnetic resonance imaging (rs-fMRI) from 489 healthy unimpaired older adults, including 46 with longitudinal data. We found significant correlations between tau in limbic network and Aβ in distinct functional networks. We then demonstrated that Aβ+ /Tau- participants exhibited elevated inter-network functional connectivity of the limbic network. Finally, our longitudinal results showed that annual increases in inter-network functional connectivity between limbic network and default mode and control networks were linked to annual tau elevation in limbic network, primarily modulated by Aβ+ individuals. Understanding this early brain alteration in response to pathologies could guide treatments early in disease course.

DOI10.1016/j.neurobiolaging.2025.01.005
Alternate JournalNeurobiol Aging
PubMed ID39879839
Grant ListK24 AG045334 / AG / NIA NIH HHS / United States
R01 AG050440 / AG / NIA NIH HHS / United States
R01 AG055299 / AG / NIA NIH HHS / United States