Genetic determinants of white matter hyperintensities and amyloid angiopathy in familial Alzheimer's disease

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Ryan, NS (Author) Other; Biessels, GJ (Author) Other; Kim, L (Author) Other; Nicholas, JM (Author) Other; Barber, PA (Author) Other; Walsh, P (Author) Other; Gami, P (Author) Other; Morris, HR (Author) Other; Bastos-Leite AJ (Author) FMUP; Schott, JM (Author) Other; Beck, J (Author) Other; Mead, S (Author) Other; Chavez Gutierrez, L (Author) Other; de Strooper, B (Author) Other; Rossor, MN (Author) Other; Revesz, T (Author) Other; Lashley, T (Author) Other; Fox, NC (Author) Other

Journal

Title: Neurobiology of Aging

Vol. 36

Pages: 3140-3151

ISSN: 0197-4580

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 50 Citations

Scopus - 49 Citations

Other information

Authenticus ID: P-00G-WGV

DOI: 10.1016/j.neurobiolaging.2015.08.026

Abstract (EN): Familial Alzheimer's disease (FAD) treatment trials raise interest in the variable occurrence of cerebral amyloid angiopathy (CAA); an emerging important factor in amyloid-modifying therapy. Previous pathological studies reported particularly severe CAA with postcodon 200 PSEN1 mutations and amyloid beta coding domain APP mutations. As CAA may manifest as white matter hyperintensities (WMH) on magnetic resonance imaging, particularly posteriorly, we investigated WMH in 52 symptomatic FAD patients for associations with mutation position. WMH were visually rated in 39 PSEN1 (18 precodon 200); 13 APP mutation carriers and 25 healthy controls. Ten PSEN1 mutation carriers (5 precodon 200) had postmortem examination. Increased WMH were observed in the PSEN1 postcodon 200 group and in the single APP patient with an amyloid beta coding domain (p.Ala692Gly, Flemish) mutation. WMH burden on MRI correlated with severity of CAA and cotton wool plaques in several areas. The precodon 200 group had younger ages at onset, decreased axonal density and/or integrity, and a greater T-lymphocytic response in occipital deep white matter. Mutation site contributes to the phenotypic and pathological heterogeneity witnessed in FAD.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12