Enhanced Abeta40 deposition was associated with increased Abeta42-43 in cerebral vasculature with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D).
Cerebrovascular deposition of the amyloid beta-protein (Abeta) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders. Such an Abeta vascular deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses, including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular Abeta deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. We analyzed cerebral Abeta deposition in brains with AD and Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) on the basis of two amyloid species of Abeta(40) and Abeta(42/43) using specific monoclonal antibodies. Compared to Abeta deposition in senile plaques, the molecular composition of Abeta was distinguishable, indicating that the Abeta(40) species is the main component for vascular amyloid. Furthermore, we found Abeta(42/43) immunoreactivity was also much increased in amyloid angiopathy of all cases with HCHWA-D. Taken together, amyloid angiopathy in HCHWA-D may share an Abeta(42)-driven deposition mechanism with plaque amyloid, resulting in enhanced Abeta(40) deposition.
Ozawa
K
K
Department of Neuroscience, Institute of Gerontology, Osaka City University, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Tomiyama
T
T
Maat-Schieman
M L
ML
Roos
R A
RA
Mori
H
H
D016229:Amyloid beta-Peptides / Q000235:genetics*; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D019556:COS Cells; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D009154:Mutation; D009426:Netherlands; D010446:Peptide Fragments / Q000235:genetics*; D013548:Sweden; D014162:Transfection
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C098994:amyloid beta-protein (1-43)