The contribution of β-amyloid, Tau and α-synuclein to blood–brain barrier damage in neurodegenerative disorders

Ying Chieh Wu, Tizibt Ashine Bogale, Jari Koistinaho, Marina Pizzi, Taisia Rolova, Arianna Bellucci

Research output: Contribution to journalReview Articlepeer-review


Central nervous system (CNS) accumulation of fibrillary deposits made of Amyloid β (Aβ), hyperphosphorylated Tau or α-synuclein (α-syn), present either alone or in the form of mixed pathology, characterizes the most common neurodegenerative diseases (NDDs) as well as the aging brain. Compelling evidence supports that acute neurological disorders, such as traumatic brain injury (TBI) and stroke, are also accompanied by increased deposition of toxic Aβ, Tau and α-syn species. While the contribution of these pathological proteins to neurodegeneration has been experimentally ascertained, the cellular and molecular mechanisms driving Aβ, Tau and α-syn-related brain damage remain to be fully clarified. In the last few years, studies have shown that Aβ, Tau and α-syn may contribute to neurodegeneration also by inducing and/or promoting blood–brain barrier (BBB) disruption. These pathological proteins can affect BBB integrity either directly by affecting key BBB components such as pericytes and endothelial cells (ECs) or indirectly, by promoting brain macrophages activation and dysfunction. Here, we summarize and critically discuss key findings showing how Aβ, Tau and α-syn can contribute to BBB damage in most common NDDs, TBI and stroke. We also highlight the need for a deeper characterization of the role of these pathological proteins in the activation and dysfunction of brain macrophages, pericytes and ECs to improve diagnosis and treatment of acute and chronic neurological disorders.

Original languageEnglish
Article number39
JournalActa Neuropathologica
Issue number1
Number of pages15
Publication statusPublished - Jun 2024
MoE publication typeA2 Review article in a scientific journal

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Fields of Science

  • Amyloid β
  • Brain macrophages
  • Endothelial cells
  • Pericytes
  • Tau
  • α-synuclein
  • 3112 Neurosciences

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