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P4‐525: ASSOCIATION OF CSF TAU WITH HYPERPLASTICITY IN ALZHEIMER'S DISEASE
Author(s) -
Visser Pieter Jelle,
Gobom Johan,
Reus Lianne M.,
Jansen Iris E.,
Tsolaki Magda,
Verhey Frans R.J.,
Popp Julius,
Martinez-Lage Pablo,
Vandenberghe Rik,
Lleó Alberto,
Molinuevo Jose Luis,
Engelborghs Sebastiaan,
Lovestone Simon,
Streffer Johannes,
Vos Stephanie J.B.,
Bos Isabelle,
Bertram Lars,
Posthuma Danielle,
Smit August B.,
Blennow Kaj,
Scheltens Philip,
Teunissen Charlotte E.,
Zetterberg Henrik,
Tijms Betty M.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.08.072
Subject(s) - biomarker , neuroscience , dementia , medicine , cognitive impairment , disease , alzheimer's disease neuroimaging initiative , psychology , neuroimaging , oncology , chemistry , cognition , biochemistry
fragments. Granzyme A-cleaved C-terminal tau fragments have increased levels of phosphorylation, are more prone to aggregate and propagate aggregation compared to tau1-441, while these phenotypes are decreased in the granzyme A-cleaved N-terminal tau fragments. However, the latter demonstrate an increased propensity to undergo transcellular spreading compared to granzyme A-cleaved C-terminal tau fragments and full-length tau1-441. Furthermore, increased amounts of cleaved, phosphorylated and aggregated tau were identified in CBD and PSP patient brains compared to age-matched controls. Cleavage sites within tau to produce granzyme A-cleaved tau fragments were identified by mass spectrometry in CBD and PSP patient brains. Conclusions: Our results show that (i) granzyme A cleaves tau to produce tauopathy-specific tau fragments, and (ii) granzyme A-cleaved tau fragments have distinct cellular effects which could play an important role in tauopathy pathogenesis. Elucidating granzyme A-cleavage of tau is crucial in unravelling tauopathy pathogenesis to identify potential therapeutic targets and diagnostic biomarkers.