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Brain Vasculature Accumulates Tau and Is Spatially Related to Tau Tangle Pathology in Alzheimer's Disease.
Hoglund, Zachary; Ruiz-Uribe, Nancy; Del Sastre, Eric; Woost, Benjamin; Bailey, Joshua; Hyman, Bradley T; Zwang, Theodore; Bennett, Rachel E.
Afiliação
  • Hoglund Z; Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
  • Ruiz-Uribe N; Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
  • Del Sastre E; Harvard Medical School, Boston, MA, USA.
  • Woost B; Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
  • Bailey J; Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
  • Hyman BT; Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
  • Zwang T; Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
  • Bennett RE; Harvard Medical School, Boston, MA, USA.
bioRxiv ; 2024 Jan 28.
Article em En | MEDLINE | ID: mdl-38328111
ABSTRACT
Insoluble pathogenic proteins accumulate along blood vessels in conditions of cerebral amyloid angiopathy (CAA), exerting a toxic effect on vascular cells and impacting cerebral homeostasis. In this work we provide new evidence from three-dimensional human brain histology that tau protein, the main component of neurofibrillary tangles, can similarly accumulate along brain vascular segments. We quantitatively assessed n=6 Alzheimer's disease (AD), and n=6 normal aging control brains and saw that tau-positive blood vessel segments were present in all AD cases. Tau-positive vessels are enriched for tau at levels higher than the surrounding tissue and appear to affect arterioles across cortical layers (I-V). Further, vessels isolated from these AD tissues were enriched for N-terminal tau and tau phosphorylated at T181 and T217. Importantly, tau-positive vessels are associated with local areas of increased tau neurofibrillary tangles. This suggests that accumulation of tau around blood vessels may reflect a local clearance failure. In sum, these data indicate tau, like amyloid beta, accumulates along blood vessels and may exert a significant influence on vasculature in the setting of AD.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article