Elevated CSF GAP-43 is Associated with Accelerated Tau Accumulation and Spread in Alzheimer's Disease

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jan 3

PMID 38172114

Authors

Nicolai Franzmeier

Amir Dehsarvi

Anna Steward

Davina Biel

Anna Dewenter

Sebastian Niclas Roemer

Fabian Wagner

Mattes Gross

Matthias Brendel

Alexis Moscoso

Prithvi Arunachalam

Kaj Blennow

Henrik Zetterberg

Michael Ewers

Michael Scholl

Affiliations

Soon will be listed here.

Abstract

In Alzheimer's disease, amyloid-beta (Aβ) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. Aβ induces aberrant synaptic activity, manifesting in increases in the presynaptic growth-associated protein 43 (GAP-43), which is closely involved in synaptic activity and plasticity. We therefore tested whether Aβ-related GAP-43 increases, as a marker of synaptic changes, drive tau spreading in 93 patients across the aging and Alzheimer's spectrum with available CSF GAP-43, amyloid-PET and longitudinal tau-PET assessments. We found that (1) higher GAP-43 was associated with faster Aβ-related tau accumulation, specifically in brain regions connected closest to subject-specific tau epicenters and (2) that higher GAP-43 strengthened the association between Aβ and connectivity-associated tau spread. This suggests that GAP-43-related synaptic changes are linked to faster Aβ-related tau spread across connected regions and that synapses could be key targets for preventing tau spreading in Alzheimer's disease.

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