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000266772 1001_ $$00000-0001-9736-2283$$aFranzmeier, Nicolai$$b0
000266772 245__ $$aElevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease.
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000266772 520__ $$aIn Alzheimer's disease, amyloid-beta (Aβ) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. Aβ induces aberrant synaptic activity, manifesting in increases in the presynaptic growth-associated protein 43 (GAP-43), which is closely involved in synaptic activity and plasticity. We therefore tested whether Aβ-related GAP-43 increases, as a marker of synaptic changes, drive tau spreading in 93 patients across the aging and Alzheimer's spectrum with available CSF GAP-43, amyloid-PET and longitudinal tau-PET assessments. We found that (1) higher GAP-43 was associated with faster Aβ-related tau accumulation, specifically in brain regions connected closest to subject-specific tau epicenters and (2) that higher GAP-43 strengthened the association between Aβ and connectivity-associated tau spread. This suggests that GAP-43-related synaptic changes are linked to faster Aβ-related tau spread across connected regions and that synapses could be key targets for preventing tau spreading in Alzheimer's disease.
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000266772 650_7 $$2NLM Chemicals$$aGAP-43 Protein
000266772 650_7 $$2NLM Chemicals$$atau Proteins
000266772 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000266772 650_7 $$2NLM Chemicals$$aBiomarkers
000266772 650_2 $$2MeSH$$aHumans
000266772 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000266772 650_2 $$2MeSH$$aGAP-43 Protein: genetics
000266772 650_2 $$2MeSH$$aGAP-43 Protein: metabolism
000266772 650_2 $$2MeSH$$atau Proteins: metabolism
000266772 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000266772 650_2 $$2MeSH$$aBrain: metabolism
000266772 650_2 $$2MeSH$$aPositron-Emission Tomography
000266772 650_2 $$2MeSH$$aCognitive Dysfunction: metabolism
000266772 650_2 $$2MeSH$$aBiomarkers: metabolism
000266772 7001_ $$00000-0001-7116-9741$$aDehsarvi, Amir$$b1
000266772 7001_ $$aSteward, Anna$$b2
000266772 7001_ $$aBiel, Davina$$b3
000266772 7001_ $$00000-0002-5636-196X$$aDewenter, Anna$$b4
000266772 7001_ $$00000-0003-3423-457X$$aRoemer, Sebastian Niclas$$b5
000266772 7001_ $$aWagner, Fabian$$b6
000266772 7001_ $$aGroß, Mattes$$b7
000266772 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b8
000266772 7001_ $$00000-0003-0170-036X$$aMoscoso, Alexis$$b9
000266772 7001_ $$aArunachalam, Prithvi$$b10
000266772 7001_ $$aBlennow, Kaj$$b11
000266772 7001_ $$00000-0003-3930-4354$$aZetterberg, Henrik$$b12
000266772 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b13
000266772 7001_ $$00000-0001-7800-1781$$aSchöll, Michael$$b14
000266772 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-44374-w$$gVol. 15, no. 1, p. 202$$n1$$p202$$tNature Communications$$v15$$x2041-1723$$y2024
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