TY - JOUR
T1 - Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations
AU - Luis, Elkin
AU - Ortiz, Alexandra
AU - Eudave, Luis
AU - Ortega-Cubero, Sara
AU - Borroni, Barbara
AU - Van Der Zee, Julie
AU - Gazzina, Stefano
AU - Caroppo, Paola
AU - Rubino, Elisa
AU - D'Agata, Federico
AU - Le Ber, Isabelle
AU - Santana, Isabel
AU - Cunha, Gil
AU - Almeida, Maria R.
AU - Boutoleau-Bretonnière, Claire
AU - Hannequin, Didier
AU - Wallon, David
AU - Rainero, Innocenzo
AU - Galimberti, Daniela
AU - Van Broeckhoven, Christine
AU - Pastor, Maria A.
AU - Pastor, Pau
PY - 2016/6/22
Y1 - 2016/6/22
N2 - Background: Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD). Objective: The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction. Methods: We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n=10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n=20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n=20). The groups were matched according to current age, disease duration, and gender. Results: After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres. Conclusions: These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.
AB - Background: Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD). Objective: The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction. Methods: We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n=10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n=20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n=20). The groups were matched according to current age, disease duration, and gender. Results: After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres. Conclusions: These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.
KW - Dementia
KW - frontotemporal dementia
KW - SQSTM1 protein
KW - voxel-based morphometry
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UR - http://www.scopus.com/inward/citedby.url?scp=84976411574&partnerID=8YFLogxK
U2 - 10.3233/JAD-160006
DO - 10.3233/JAD-160006
M3 - Article
AN - SCOPUS:84976411574
VL - 53
SP - 303
EP - 313
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 1
M1 - JAD160006
ER -