title: White matter changes in familial Alzheimer's disease.
abstract: BACKGROUND
  Familial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 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.
  
  
  METHODS
  Ten mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 noncarriers (NCs) were included in the study. Three MCs were symptomatic and seven were presymptomatic (pre-MCs).
  
  
  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 MCs and NCs. 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-MCs compared with NCs. After inclusion of the three symptomatic MCs 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-tau181p 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.
authors: Karolinska Institutet, Department of Neurobiology, Care Science and Society (NVS), Division of Clinical Geriatrics, Stockholm, Sweden.
authors: X
authors: X
authors: Li
authors: Karolinska Institutet, Department of Neurobiology, Care Science and Society (NVS), Division of Clinical Geriatrics, Stockholm, Sweden.
authors: E
authors: E
authors: Westman
authors: Karolinska Institutet, Department of NVS, Division of Neurogeriatrics, Center for Alzheimer Disease Research, Huddinge, Stockholm, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: A K
authors: AK
authors: Ståhlbom
authors: Karolinska Institutet, Department of NVS, Division of Neurogeriatrics, Center for Alzheimer Disease Research, Huddinge, Stockholm, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: S
authors: S
authors: Thordardottir
authors: Karolinska Institutet, Department of Neurobiology, Care Science and Society (NVS), Division of Clinical Geriatrics, Stockholm, Sweden.|Stockholm University, Department of Psychology, Stockholm, Sweden.
authors: O
authors: O
authors: Almkvist
authors: Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: K
authors: K
authors: Blennow
authors: Karolinska Institutet, Department of Neurobiology, Care Science and Society (NVS), Division of Clinical Geriatrics, Stockholm, Sweden.
authors: L-O
authors: LO
authors: Wahlund
authors: Karolinska Institutet, Department of NVS, Division of Neurogeriatrics, Center for Alzheimer Disease Research, Huddinge, Stockholm, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: C
authors: C
authors: Graff
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
keywords: cerebrospinal fluid biomarkers; diffusion tensor imaging; familial Alzheimer's disease; mutation carriers; white matter changes