Journal Article

DZNE-2024-00035

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease.

Franzmeier, N. ; Dehsarvi, A. ; Steward, A. ; Biel, D. ; Dewenter, A. ; Roemer, S. N. ; Wagner, F. ; Groß, M. ; Brendel, M.Extern* ; Moscoso, A. ; Arunachalam, P. ; Blennow, K. ; Zetterberg, H. ; Ewers, M.DZNE* ; Schöll, M.

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-44374-w

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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; GAP-43 Protein: genetics (MeSH) ; GAP-43 Protein: metabolism (MeSH) ; tau Proteins: metabolism (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Positron-Emission Tomography (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Biomarkers: metabolism (MeSH) ; GAP-43 Protein ; tau Proteins ; Amyloid beta-Peptides ; Biomarkers

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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