Cerebral vascular accumulation of Dutch-type Aβ42, but not wild-type Aβ42, in hereditary cerebral hemorrhage with amyloidosis, Dutch type

✍ Scribed by Kazuchika Nishitsuji; Takami Tomiyama; Kenichi Ishibashi; Fuyuki Kametani; Kazuharu Ozawa; Ryota Okada; Marion L. Maat-Schieman; Raymund A.C. Roos; Kazuhiro Iwai; Hiroshi Mori

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 284 KB
• Volume: 85
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21413

✦ Synopsis

Abstract

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA‐D), is an autosomal dominant disorder caused by the Dutch mutation (E693Q) in the β‐amyloid precursor protein. This mutation produces an aberrant amyloid β (Aβ) species (AβE22Q) and causes severe meningocortical vascular Aβ deposition. We analyzed the Aβ composition of the vascular amyloid in the brains of HCHWA‐D patients. Immunohistochemistry demonstrated that the vascular amyloid contained both Aβ40 and Aβ42, with a high Aβ40/Aβ42 ratio. In Western blotting of cerebral microvessel fractions isolated from the brains, both wild‐type and Dutch‐type Aβ40 were observed as major species. Reverse‐phase HPLC‐mass spectrometric analysis of the fractions revealed both wild‐type and Dutch‐type Aβ38 as the other main components of the vascular amyloid. Moreover, we detected peaks corresponding to Dutch‐type Aβ42 but not to wild‐type Aβ42. These results suggest a pathogenic role for the mutant Aβ42 in addition to the mutant Aβ40 in the cerebral amyloid angiopathy of HCHWA‐D. © 2007 Wiley‐Liss, Inc.