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

Autor: Tammaryn Lashley, Jon Beck, Bart De Strooper, Phoebe Walsh, Huw R. Morris, Lois G. Kim, Martin N. Rossor, Jennifer M. Nicholas, Geert Jan Biessels, Simon Mead, Lucía Chávez-Gutiérrez, P Gami, Philip A. Barber, Nick C. Fox, António J. Bastos-Leite, Natalie S. Ryan, Jonathan M. Schott, Tamas Revesz
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Aging
Pathology
Presenilin 1 (PSEN1
PS1)
Amyloid beta-Protein Precursor
Amyloid precursor protein
PSEN1
White matter hyperintensities
Medicine
Non-U.S. Gov't
biology
General Neuroscience
Research Support
Non-U.S. Gov't
Middle Aged
Magnetic Resonance Imaging
White Matter
medicine.anatomical_structure
Female
Cerebral amyloid angiopathy
Alzheimer's disease
Adult
medicine.medical_specialty
Amyloid beta
Neuroscience(all)
Clinical Neurology
Presenilin 1 (PSEN1
Research Support
Presenilin
White matter
Apolipoproteins E
PS1)
Alzheimer Disease
mental disorders
Presenilin-1
Journal Article
Humans
Codon
Amyloid precursor protein (APP)
Retrospective Studies
Familial Alzheimer's disease
business.industry
medicine.disease
Hyperintensity
Ageing
Mutation
biology.protein
Neurology (clinical)
Geriatrics and Gerontology
business
Developmental Biology
Zdroj: Neurobiology of Aging, 36(12), 3140. Elsevier Inc.
ISSN: 0197-4580
Popis: 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.
Databáze: OpenAIRE
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