Role of blood vessels in producing pathological changes in the brain with Alzheimer's disease.
Vascular factors have been shown to be highly involved in the deposition of the amyloid beta-protein (A beta) in the brain of Alzheimer's disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of A beta 40 and A beta 42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of A beta 40 and A beta 42 in sera between sporadic AD and controls, a certain dysfunction of the blood-brain barrier could induce an abnormal transport of A beta from sera to the parenchyma in AD. In addition, vascular A beta deposits and mature A beta plaques stained by Congo red in AD brains contained more A beta 40 than A beta 42, whereas Congo red-negative immature plaques mainly consisted of A beta 42. Our confocal laser scanning microscopy demonstrated an intimate relationship between A beta 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 A beta 40 and/or A beta 42 cause A beta 40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of A beta 40, (2) selective transport A beta 40 and A beta 42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of A beta 42 into A beta 40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in A beta fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of A beta 40 associated with blood vessels may play a critical role in the development of AD.
Miyakawa
T
T
Department of Neuropsychiatry, Kumamoto University School of Medicine, Japan. psychiat@kaiju.medic.kumamoto-u.ac.jp
Kimura
T
T
Hirata
S
S
Fujise
N
N
Ono
T
T
Ishizuka
K
K
Nakabayashi
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001808:Blood Vessels / Q000473:pathology*; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D058225:Plaque, Amyloid / Q000473:pathology / Q000648:ultrastructure; D012016:Reference Values
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)