%0 Journal Article
%A Franzmeier, Nicolai
%A Dehsarvi, Amir
%A Steward, Anna
%A Biel, Davina
%A Dewenter, Anna
%A Roemer, Sebastian Niclas
%A Wagner, Fabian
%A Groß, Mattes
%A Brendel, Matthias
%A Moscoso, Alexis
%A Arunachalam, Prithvi
%A Blennow, Kaj
%A Zetterberg, Henrik
%A Ewers, Michael
%A Schöll, Michael
%T Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease.
%J Nature Communications
%V 15
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DZNE-2024-00035
%P 202
%D 2024
%X 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.
%K Humans
%K Alzheimer Disease: metabolism
%K GAP-43 Protein: genetics
%K GAP-43 Protein: metabolism
%K tau Proteins: metabolism
%K Amyloid beta-Peptides: metabolism
%K Brain: metabolism
%K Positron-Emission Tomography
%K Cognitive Dysfunction: metabolism
%K Biomarkers: metabolism
%K GAP-43 Protein (NLM Chemicals)
%K tau Proteins (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC10764818
%$ pmid:38172114
%R 10.1038/s41467-023-44374-w
%U https://pub.dzne.de/record/266772