TY  - JOUR
AU  - Franzmeier, Nicolai
AU  - Dehsarvi, Amir
AU  - Steward, Anna
AU  - Biel, Davina
AU  - Dewenter, Anna
AU  - Roemer, Sebastian Niclas
AU  - Wagner, Fabian
AU  - Groß, Mattes
AU  - Brendel, Matthias
AU  - Moscoso, Alexis
AU  - Arunachalam, Prithvi
AU  - Blennow, Kaj
AU  - Zetterberg, Henrik
AU  - Ewers, Michael
AU  - Schöll, Michael
TI  - Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2024-00035
SP  - 202
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: metabolism
KW  - GAP-43 Protein: genetics
KW  - GAP-43 Protein: metabolism
KW  - tau Proteins: metabolism
KW  - Amyloid beta-Peptides: metabolism
KW  - Brain: metabolism
KW  - Positron-Emission Tomography
KW  - Cognitive Dysfunction: metabolism
KW  - Biomarkers: metabolism
KW  - GAP-43 Protein (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10764818
C6  - pmid:38172114
DO  - DOI:10.1038/s41467-023-44374-w
UR  - https://pub.dzne.de/record/266772
ER  -