Department of Neuropsychiatry, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan
Vascular factors have been shown to be highly involved in the
deposition of the amyloid ß-protein (Aß)
in the brain of Alzheimer's disease (AD). However, the detailed
mechanism remains unknown. Here, we showed that more numerous
deposits of Aß
40 and Aß
42 in the brain were
found in AD patients than in controls. Together with evidence
of no difference in the level of Aß
40 and Aß
42 in sera between sporadic AD and conrols, a certain dysfunction
of the blood-brain barrier could induce an abnormal transport
of Aß from sera to the parenchyma in AD. In addition,
vascular Aß deposits and mature Aß plaques
stained by Congo red in AD brains contained more Aß
40 than Aß
42, whereas Congo red-negative immature plaques
mainly consisted of Aß42. Our confocal laser scanning
microscopy demonstrated an intimate relationship between Aß
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 Aß
40 and/or Aß
42 cause Aß
40 deposition in and around blood vessels through unknown but possible
mechanisms such as (1) endocytosis of Aß
40, (2) selective
transport Aß
40 and Aß
42 into blood vessels
and the parenchyma, respectively, and (3) proteolysis of Aß
42 into Aß
40 induced by a putative carboxyl dipeptidase
in blood vessels including vascular feet, which is involved
in Aß fibrillation and cognitive deterioration in
the patients. Therefore, the accumulation of Aß
40 associated with blood vessels may play a critical role in the
development of AD.
