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White matter changes in familial Alzheimer's disease
Author(s) -
Li X.,
Westman E.,
Ståhlbom A. K.,
Thordardottir S.,
Almkvist O.,
Blennow K.,
Wahlund L.O.,
Graff C.
Publication year - 2015
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12352
Subject(s) - medicine , white matter , disease , alzheimer's disease , white (mutation) , pathology , genetics , magnetic resonance imaging , radiology , biology , gene
Background Familial Alzheimer's disease ( FAD ) resulting from gene mutations in PSEN 1 , PSEN 2 and APP is associated with changes in the brain. Objective The aim of this study was to investigate changes in grey matter ( GM ), white matter ( WM ) and the cerebrospinal fluid ( CSF ) in FAD . Subjects Ten mutation carriers ( MC s) with three different mutations in PSEN 1 and APP and 20 noncarriers ( NC s) were included in the study. Three MC s were symptomatic and seven were presymptomatic (pre‐ MC s). Methods Whole‐brain GM volume as well as fractional anisotropy ( FA ) and mean diffusivity ( MD ) using voxel‐based morphometry and tract‐based spatial statistics analyses, respectively, were compared between MC s and NC s. FA and MD maps were obtained from diffusion tensor imaging. Results A significant increase in MD was found in the left inferior longitudinal fasciculus, cingulum and bilateral superior longitudinal fasciculus in pre‐ MC s compared with NC s. After inclusion of the three symptomatic MC s in the analysis, the regions became wider. The mean MD of these regions showed significant negative correlation with the CSF level of Aβ42, and positive correlations with P‐tau 181p and T‐tau. No differences were observed in GM volume and FA between the groups. Conclusions The results of this study suggest that FAD gene mutations affect WM diffusivity before changes in GM volume can be detected. The WM changes observed were related to changes in the CSF , with similar patterns previously observed in sporadic Alzheimer's disease.