Role of blood vessels in producing pathological changes in the brain with Alzheimer's disease

Taihei Miyakawa, Takemi Kimura, Shinichi Hirata, Noboru Fujise, Tsunehiko Ono, Koko Ishizuka, Jun Nakabayashi

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular factors have been shown to be highly involved in the deposition of the amyloid β-protein (Aβ) in the brain of Alzheimer's disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of Aβ40 and Aβ42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of Aβ40 and Aβ42 in sera between sporadic AD and conrols, a certain dysfunction of the blood-brain barrier could induce an abnormal transport of Aβ from sera to the parenchyma in AD. In addition, vascular Aβ deposits and mature Aβ plaques stained by Congo red in AD brains contained more Aβ40 than Aβ42, whereas Congo red-negative immature plaques mainly consisted of Aβ42. Our confocal laser scanning microscopy demonstrated an intimate relationship between Aβ40 and the vascular network. The amount of mature plaques but not that of immature plaques was reportedly correlated with the severity of dementia in AD patients. These results suggest that serum-derived Aβ40 and/or Aβ42 cause Aβ40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of Aβ40, (2) selective transport Aβ40 and Aβ42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of Aβ42 into Aβ40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in Aβ fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of Aβ40 associated with blood vessels may play a critical role in the development of AD.

Original languageEnglish (US)
Pages (from-to)46-54
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume903
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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