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@ARTICLE{Franzmeier:266772,
author = {Franzmeier, Nicolai and Dehsarvi, Amir and Steward, Anna
and Biel, Davina and Dewenter, Anna and Roemer, Sebastian
Niclas and Wagner, Fabian and Groß, Mattes and Brendel,
Matthias and Moscoso, Alexis and Arunachalam, Prithvi and
Blennow, Kaj and Zetterberg, Henrik and Ewers, Michael and
Schöll, Michael},
title = {{E}levated {CSF} {GAP}-43 is associated with accelerated
tau accumulation and spread in {A}lzheimer's disease.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2024-00035},
pages = {202},
year = {2024},
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.},
keywords = {Humans / Alzheimer Disease: metabolism / GAP-43 Protein:
genetics / GAP-43 Protein: metabolism / tau Proteins:
metabolism / Amyloid beta-Peptides: metabolism / Brain:
metabolism / Positron-Emission Tomography / Cognitive
Dysfunction: metabolism / Biomarkers: metabolism / GAP-43
Protein (NLM Chemicals) / tau Proteins (NLM Chemicals) /
Amyloid beta-Peptides (NLM Chemicals) / Biomarkers (NLM
Chemicals)},
cin = {Clinical Research (Munich)},
ddc = {500},
cid = {I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10764818},
pubmed = {pmid:38172114},
doi = {10.1038/s41467-023-44374-w},
url = {https://pub.dzne.de/record/266772},
}