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

Line Andersen Lunau; Kim Mouridsen; Anders Rodell; Jørgen Nielsen; Adrian Isaacs; Jerry Brown; Dora Zeidler; Leif Østergaard; Simon Fristed Eskildsen; Elisabet Englund; Peter Johannsen

doi:10.1016/j.jalz.2010.05.053

Abstract

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 language	English
Publication date	Jul 2010
DOIs	https://doi.org/10.1016/j.jalz.2010.05.053
Publication status	Published - Jul 2010
Event	International Conference on Alzheimer's Disease - Honolulu, United States Duration: 10 Jul 2010 → 15 Jul 2010

Conference

Conference	International Conference on Alzheimer's Disease
Country/Territory	United States
City	Honolulu
Period	10/07/2010 → 15/07/2010

Keywords

FTD
CBF
MRI

Access to Document

10.1016/j.jalz.2010.05.053

http://www.alzheimersanddementia.com/article/S1552-5260(10)00173-1/fulltext

Cite this

Lunau, L. A., Mouridsen, K., Rodell, A., Nielsen, J., Isaacs, A., Brown, J., Zeidler, D., Østergaard, L., Eskildsen, S. F., Englund, E., & Johannsen, P. (2010). Changes in Cerebral Blood Flow in Presymptomatic Mutation Carriers of Familial Frontotemporal Dementia (FTD-3), Measured with MRI. Abstract from International Conference on Alzheimer's Disease, Honolulu, United States. https://doi.org/10.1016/j.jalz.2010.05.053

@conference{1ffe9cc130f449d084e2a79fd2a749ca,

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

abstract = "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.",

keywords = "FTD, CBF, MRI",

author = "Lunau, {Line Andersen} and Kim Mouridsen and Anders Rodell and J{\o}rgen Nielsen and Adrian Isaacs and Jerry Brown and Dora Zeidler and Leif {\O}stergaard and Eskildsen, {Simon Fristed} and Elisabet Englund and Peter Johannsen",

year = "2010",

month = jul,

doi = "10.1016/j.jalz.2010.05.053",

language = "English",

note = "International Conference on Alzheimer's Disease, ICAD2010 ; Conference date: 10-07-2010 Through 15-07-2010",

}

Lunau, LA, Mouridsen, K, Rodell, A, Nielsen, J, Isaacs, A, Brown, J, Zeidler, D , Østergaard, L , Eskildsen, SF, Englund, E & Johannsen, P 2010, 'Changes in Cerebral Blood Flow in Presymptomatic Mutation Carriers of Familial Frontotemporal Dementia (FTD-3), Measured with MRI', International Conference on Alzheimer's Disease, Honolulu, United States, 10/07/2010 - 15/07/2010. https://doi.org/10.1016/j.jalz.2010.05.053

Changes in Cerebral Blood Flow in Presymptomatic Mutation Carriers of Familial Frontotemporal Dementia (FTD-3), Measured with MRI. / Lunau, Line Andersen; Mouridsen, Kim; Rodell, Anders et al.
2010. Abstract from International Conference on Alzheimer's Disease, Honolulu, United States.

Research output: Contribution to conference › Conference abstract for conference › Research › peer-review

TY - ABST

T1 - Changes in Cerebral Blood Flow in Presymptomatic Mutation Carriers of Familial Frontotemporal Dementia (FTD-3), Measured with MRI

AU - Lunau, Line Andersen

AU - Mouridsen, Kim

AU - Rodell, Anders

AU - Nielsen, Jørgen

AU - Isaacs, Adrian

AU - Brown, Jerry

AU - Zeidler, Dora

AU - Østergaard, Leif

AU - Eskildsen, Simon Fristed

AU - Englund, Elisabet

AU - Johannsen, Peter

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

KW - FTD

KW - CBF

KW - MRI

U2 - 10.1016/j.jalz.2010.05.053

DO - 10.1016/j.jalz.2010.05.053

M3 - Conference abstract for conference

T2 - International Conference on Alzheimer's Disease

Y2 - 10 July 2010 through 15 July 2010

ER -