Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease

Franzmeier, Nicolai; Dehsarvi, Amir; Steward, Anna; Biel, Davina; Dewenter, Anna; Roemer, Sebastian Niclas; Wagner, Fabian; Gross, Mattes; Brendel, Matthias; Moscoso, Alexis; Arunachalam, Prithvi; Blennow, Kaj; Zetterberg, Henrik; Ewers, Michael und Schoell, Michael (2024): Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease. In: Nature Communications, Bd. 15, Nr. 1, 202

Abstract

In Alzheimer's disease, amyloid-beta (A beta) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. A beta 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 A beta-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 A beta-related tau accumulation, specifically in brain regions connected closest to subject-specific tau epicenters and (2) that higher GAP-43 strengthened the association between A beta and connectivity-associated tau spread. This suggests that GAP-43-related synaptic changes are linked to faster A beta-related tau spread across connected regions and that synapses could be key targets for preventing tau spreading in Alzheimer's disease. Trans-synaptic tau spread drives neurodegeneration in Alzheimer's disease. This study shows that GAP-43, a marker of synaptic abnormality, is linked to faster tau spread, showing that synaptic changes may contribute to tau spreading in Alzheimer's disease.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198