TY - JOUR
T1 - Estrogen-related receptor gene expression associates with sex differences in cortical atrophy in isolated REM sleep behavior disorder
AU - Filiatrault, Marie
AU - Ayral, Violette
AU - Tremblay, Christina
AU - Haddad, Celine
AU - Daneault, Véronique
AU - Pastor-Bernier, Alexandre
AU - Gagnon, Jean François
AU - Postuma, Ronald B.
AU - Dušek, Petr
AU - Mareček, Stanislav
AU - Varga, Zsoka
AU - Klein, Johannes C.
AU - Hu, Michele T.
AU - Arnulf, Isabelle
AU - Dodet, Pauline
AU - Vidailhet, Marie
AU - Corvol, Jean Christophe
AU - Lehéricy, Stéphane
AU - ICEBERG Study Group
AU - Lewis, Simon
AU - Matar, Elie
AU - Ehgoetz Martens, Kaylena A.
AU - Churchill, Lachlan
AU - Borghammer, Per
AU - Knudsen, Karoline
AU - Hansen, Allan K.
AU - Arnaldi, Dario
AU - Orso, Beatrice
AU - Mattioli, Pietro
AU - Roccatagliata, Luca
AU - Rahayel, Shady
N1 - Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2025/10/10
Y1 - 2025/10/10
N2 - Isolated REM sleep behavior disorder, characterized by dream-enacting movements during REM sleep, is a male-predominant parasomnia and the strongest prodromal marker of synucleinopathies. Individuals with this disorder show cortical atrophy whose regional distribution covaries with gene expression patterns measured in the healthy human brain. However, the effect of sex on these brain changes remains unknown. The study objective is to comprehensively assess sex differences in cortical morphology and to characterize the healthy-brain gene expression correlates of brain abnormalities using the largest international multicentric MRI dataset of polysomnography-confirmed patients. Males have significantly more extensive and severe cortical thinning compared to females, despite similar age and clinical features. Imaging transcriptomics analyses indicate that regions affected in female patients map onto areas with higher expression of estrogen-related receptor genes, particularly ESRRG and ESRRA, in the healthy brain. These findings support potential sex-specific neuroprotection in the prodromal stages of synucleinopathies and may inform personalized and targeted therapeutic strategies.
AB - Isolated REM sleep behavior disorder, characterized by dream-enacting movements during REM sleep, is a male-predominant parasomnia and the strongest prodromal marker of synucleinopathies. Individuals with this disorder show cortical atrophy whose regional distribution covaries with gene expression patterns measured in the healthy human brain. However, the effect of sex on these brain changes remains unknown. The study objective is to comprehensively assess sex differences in cortical morphology and to characterize the healthy-brain gene expression correlates of brain abnormalities using the largest international multicentric MRI dataset of polysomnography-confirmed patients. Males have significantly more extensive and severe cortical thinning compared to females, despite similar age and clinical features. Imaging transcriptomics analyses indicate that regions affected in female patients map onto areas with higher expression of estrogen-related receptor genes, particularly ESRRG and ESRRA, in the healthy brain. These findings support potential sex-specific neuroprotection in the prodromal stages of synucleinopathies and may inform personalized and targeted therapeutic strategies.
UR - http://www.scopus.com/inward/record.url?scp=105018399190&partnerID=8YFLogxK
U2 - 10.1038/s41467-025-63829-w
DO - 10.1038/s41467-025-63829-w
M3 - Article
C2 - 41073384
AN - SCOPUS:105018399190
SN - 2041-1723
VL - 16
SP - 1
EP - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 9016
ER -