articleNature MedicineFeb 1, 2025HYBRID OA

Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease

TITohidul IslamEHEmily HillEEEric E. AbrahamsonSSStijn ServaesDSDenis S. Smirnov

University of Gothenburg · University of Warwick · +13 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Abstract Patients with Alzheimer’s disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. We show that Tris-buffered saline-soluble tau aggregates from autopsy-verified AD brain tissues include the core sequence ~tau 258–368 . In neuropathological assessments, antibodies against the phosphorylation sites serine-262 and serine-356 within the STA core almost exclusively stained granular (that is, prefibrillar) tau…

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50
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Authors

28

Topics & keywords

Topics
Keywords
  • Tangle
  • Serine
  • Neurofibrillary tangle
  • Disease
  • Neuroscience
  • Neurodegeneration
  • Medicine
  • Alzheimer's disease
UN Sustainable Development Goals
  • Good health and well-being
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