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Role of Blood Vessels in Producing Pathological Changes in the Brain with Alzheimer's Disease
Author(s) -
MIYAKAWA TAIHEI,
KIMURA TAKEMI,
HIRATA SHINICHI,
FUJISE NOBORU,
ONO TSUNEHIKO,
ISHIZUKA KOKO,
NAKABAYASHI JUN
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06349.x
Subject(s) - beta (programming language) , pathology , parenchyma , blood–brain barrier , amyloid beta , congo red , alzheimer's disease , cerebral amyloid angiopathy , medicine , amyloid (mycology) , degenerative disease , dementia , disease , chemistry , central nervous system , organic chemistry , adsorption , computer science , programming language
A bstract : 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 Aβ 40 and Aβ 42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of Aβ 40 and Aβ 42 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 Aβ 40 than Aβ 42 , whereas Congo red‐negative immature plaques mainly consisted of Aβ42. Our confocal laser scanning microscopy demonstrated an intimate relationship between Aβ 40 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 Aβ 40 and/or Aβ 42 cause Aβ 40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of Aβ 40 , (2) selective transport Aβ 40 and Aβ 42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of Aβ 42 into Aβ 40 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 Aβ 40 associated with blood vessels may play a critical role in the development of AD.