Cerebral microvascular accumulation of tau oligomers in Alzheimer's disease and related tauopathies

Diana L. Castillo-Carranza, Ashley N. Nilson, Candice E. Van Skike, Jordan B. Jahrling, Kishan Patel, Prajesh Garach, Julia E. Gerson, Urmi Sengupta, Jose Abisambra, Peter Nelson, Juan Troncoso, Zoltan Ungvari, Veronica Galvan, Rakez Kayed

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The importance of vascular contributions to cognitive impairment and dementia (VCID) associated with Alzheimer's disease (AD) and related neurodegenerative diseases is increasingly recognized, however, the underlying mechanisms remain obscure. There is growing evidence that in addition to Aß deposition, accumulation of hyperphosphorylated oligomeric tau contributes significantly to AD etiology. Tau oligomers are toxic and it has been suggested that they propagate in a "prion-like" fashion, inducing endogenous tau misfolding in cells. Their role in VCID, however, is not yet understood. The present study was designed to determine the severity of vascular deposition of oligomeric tau in the brain in patients with AD and related tauopathies, including dementia with Lewy bodies (DLB) and progressive supranuclear palsy (PSP). Further, we examined a potential link between vascular deposition of fibrillar Aß and that of tau oligomers in the Tg2576 mouse model. We found that tau oligomers accumulate in cerebral microvasculature of human patients with AD and PSP, in association with vascular endothelial and smooth muscle cells. Cerebrovascular deposition of tau oligomers was also found in DLB patients. We also show that tau oligomers accumulate in cerebral microvasculature of Tg2576 mice, partially in association with cerebrovascular Aß deposits. Thus, our findings add to the growing evidence for multifaceted microvascular involvement in the pathogenesis of AD and other neurodegenerative diseases. Accumulation of tau oligomers may represent a potential novel mechanism by which functional and structural integrity of the cerebral microvessels is compromised.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalAging and Disease
Volume8
Issue number3
DOIs
StatePublished - 2017

Keywords

  • Alzheimer's disease
  • Brain vascular dysfunction
  • Cerebrovascular dysfunction
  • Cerebrovasculature
  • Oligomers
  • Tau
  • Tauopathies

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

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