Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): decreased plasma amyloid-beta 42 concentration.
Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is a rare autosomal dominant disorder caused by an amyloid-beta precursor protein (AbetaPP) 693 mutation that clinically leads to recurrent hemorrhagic strokes and dementia. The disease is pathologically characterised by the deposition of Abeta in cerebral blood vessels and as plaques in the brain parenchyma. This study measured the Abeta40 and Abeta42 concentration in plasma of Dutch AbetaPP693 mutation carriers and controls. We found that the Abeta40 concentration was not different between AbetaPP693 mutation carriers and controls. However, the Abeta42 concentration was significantly decreased in the mutation carriers. No correlation exists between the APOE(epsilon)4 allele and the plasma of Abeta40 and Abeta42 levels in HCHWA-D patients. This finding contrasted with the increased concentrations found in Alzheimer's disease. Therefore it is suggested that the Dutch AbetaPP693 mutation located within the Abeta coding region of the AbetaPP gene has a different effect not only on clinical and pathological expression but also on Abeta processing.
Bornebroek
Marjolijn
M
Department of Neurology K5Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. Bornebroek@lumc.nl.
De Jonghe
Chris
C
Haan
Joost
J
Kumar-Singh
Samir
S
Younkin
Steve
S
Roos
Raymund
R
Van Broeckhoven
Christine
C
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D028243:Cerebral Amyloid Angiopathy, Familial / Q000097:blood* / Q000235:genetics*; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)