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 |
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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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