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Changes in Cerebral Blood Flow in Presymptomatic Mutation Carriers of Familial Frontotemporal Dementia (FTD-3), Measured with MRI

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  • Line Andersen Lunau, Denmark
  • Kim Mouridsen
  • Anders Rodell, Denmark
  • Jørgen Nielsen, Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark
  • Adrian Isaacs, MRC Prion Unit, Institute of Neurology, United Kingdom
  • Jerry Brown, Department of Neurology, Addenbrooke's Hospital, United States
  • Dora Zeidler
  • Leif Østergaard
  • Simon Fristed Eskildsen
  • Elisabet Englund, Lund University, Sweden
  • Peter Johannsen, Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark
Background: Frontotemporal dementia linked to chromosome 3 (FTD-3) is an autosomal dominantly inherited neurodegenerative disease caused by a truncating mutation in CHMP2B (1). The disease is characterized by insidious and progressive changes in personality, behaviour and cognition (2). The protein CHMP2B is a part of the ESCRTIII complex necessary for endosomal trafficking and protein degradation (1,3). Studies in presymptomatic CHMP2B-mutation carriers have shown both localized cortical (4) and more generalized brain atrophy (5). The purpose of this study is to assess functional change in the presymptomatic stage of the disease as indicated by local changes in cerebral blood flow (CBF). Methods: Presymptomatic mutation carriers and first-degree related non-carriers were MRI-scanned with a spin-echo sequence sensitive mainly to CBF in capillaries. CBF images were co-registered to structural T1-images (6). Perfusion data were extracted from 9 regions-of-interest (ROIs), normalized to white matter, and statistically compared between carriers and non-carriers. The Montreal Brain Template defined the 9 ROIs, which were preselected based on the previous studies of structural changes: including frontal, temporal, parietal, and occipital lobes, hippocampus, basal ganglia and cerebellum. Data were normalized to white matter in order to smooth inter-individual differences. Results: We included 8 carriers and 7 first-degree related family non-carriers. Comparing carriers with non-carriers, the former showed decreased mean CBF values at the capillary level in all ROIs, with significant changes in capillary CBF in the parietal (mean change 14 %; p = 0.03) and occipital (mean change 9 %; p = 0.02) lobes. Conclusions: Decreased cerebral blood flow can be measured in presymptomatic CHMP2B mutation carriers with statistically significant differences in the occipital- and parietal lobes. Alterations in CBF possibly affect the whole brain. Data indicate that FTD-3 pathology might involve brain capillaries. This may impact the understanding of the pathogenesis involving endosomal dysfunction and implicates involvement of the vasculature in FTD-3 pathobiology.
Original languageEnglish
Publication yearJul 2010
Publication statusPublished - Jul 2010
EventInternational Conference on Alzheimer's Disease - Honolulu, United States
Duration: 10 Jul 201015 Jul 2010


ConferenceInternational Conference on Alzheimer's Disease
CountryUnited States

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