Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer’s disease

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer’s disease
Συγγραφείς: Ying Luan, Weiyi Wang, Qi Huang, Yan Wang, Jana Nussbaumer, Jie Wang, Anna Steward, Sebastian N. Roemer-Cassiano, Yihui Guan, Michael Ewers, Michael Schöll, Ruiqing Ni, Binyin Li, Nicolai Franzmeier, Fang Xie
Πηγή: Nature Communications, Vol 16, Iss 1, Pp 1-17 (2025)
Στοιχεία εκδότη: Nature Portfolio, 2025.
Έτος έκδοσης: 2025
Συλλογή: LCC:Science
Θεματικοί όροι: Science
Περιγραφή: Abstract Synaptic loss strongly correlates with cognitive impairment in Alzheimer’s disease (AD), yet the mechanism linking its origin and pattern remain unclear. Given that connected brain regions share molecular and synaptic features, and pathological tau, a key driver of synaptic degeneration, propagates through brain networks, we hypothesize that network architecture may influence synaptic loss in AD. By combining synaptic vesicle glycoprotein 2 A (SV2A) PET in 91 AD patients and 54 controls with normative connectome data, we show strongly connected regions exhibit similar levels of synaptic loss, and synaptic loss in one region is associated with connectivity-weighted synaptic loss in connected regions. Regions strongly connected to the epicenter show greater and faster synaptic loss. Plasma p-tau181 levels correlate with network-constrained synaptic loss, and post-mortem data confirm reduced SV2A expression in tau-rich areas. These findings support that synaptic vulnerability in AD is partially constrained by network topology and is modulated by phosphorylated tau.
Τύπος εγγράφου: article
Περιγραφή αρχείου: electronic resource
Γλώσσα: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-025-61497-4
Σύνδεσμος πρόσβασης: https://doaj.org/article/e79b04de0b9548a1b465cdecb382a82c
Αριθμός Καταχώρησης: edsdoj.79b04de0b9548a1b465cdecb382a82c
Βάση Δεδομένων: Directory of Open Access Journals
Περιγραφή
ISSN:20411723
DOI:10.1038/s41467-025-61497-4