2025-09-03 国立長寿医療研究センター
図1.アルツハイマー病発症にいたるまでの脳病理の進行と血液バイオマーカーリン酸化タウの変化
<関連情報>
- https://www.ncgg.go.jp/ri/report/20250825.html
- https://www.ncgg.go.jp/ri/report/documents/20250825_KMI.pdf
- https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00974-X
バイオマーカー関連リン酸化タウ217は、前臨床アルツハイマー病の大脳皮質においてタウ線維形成に先行し、Aβ斑周囲シナプスに現れる Biomarker-related phospho-tau217 appears in synapses around Aβ plaques prior to tau tangle in cerebral cortex of preclinical Alzheimer’s disease
Yu Hirota ∙ Yasufumi Sakakibara ∙ Maho Morishima ∙ … ∙ Yuko Saito ∙ Michiko Sekiya ∙ Koichi M. Iijima
Cell Reports Published:September 2, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.116203
Highlights
- p-tau217 signals appear around Aβ plaques in synapses in preclinical AD brains
- p-tau217 colocalizes with p-tau202/205 and 231 in p-tau181-expressing axons
- p-tau217-bearing synapses are enriched with tau kinases and not engulfed by glia
- p-tau217 represents a neuronal/synaptic reaction to Aβ plaques in preclinical AD
Summary
Phospho-tau protein p-tau181 is a cerebrospinal fluid biomarker for Alzheimer’s disease (AD), while p-tau217 is the most sensitive plasma biomarker for cerebral amyloid β (Aβ) load prior to tau pathology in preclinical AD. Diagnostic and prognostic use of these p-tau biomarkers requires neuropathological interpretation. Here, we analyzed the cellular localization of biomarker p-tau species in postmortem human brains harboring different extents of Aβ plaque and tau pathology. Signals for p-tau217 were absent in normal brains but present in pre- and post-synapses surrounding Aβ plaques in preclinical AD brains. p-Tau217 colocalized with tau pathology markers p-tau202/205, p-tau231, and p-tau262, while p-tau181 was normally present in glutamatergic and GABAergic axons, which were distorted around Aβ plaques, where p-tau217 and p-tau181 colocalized. p-tau217-containing pre-synapses were enriched with active tau kinases and were not preferentially engulfed by glial cells. Emergence of p-tau217 represents a neuronal/synaptic reaction to Aβ plaques in preclinical AD brains.
