Estrogen-related receptor gene expression associates with sex differences in cortical atrophy in isolated REM sleep behavior disorder
Abstract
Abstract 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.
Article Details
Authors (35)
Marie Filiatrault
Violette Ayral
Christina Tremblay
Celine Haddad
Véronique Daneault
Alexandre Pastor-Bernier
Jean-François Gagnon
Ronald B. Postuma
Petr Dušek
Stanislav Mareček
Zsoka Varga
Johannes C. Klein
Michele T. Hu
Isabelle Arnulf
Sleep Disorder Unit, Pitié-Salpêtrière Hospital, Assistance Publique-Hopitaux de Paris
Pauline Dodet
Marie Vidailhet
Jean-Christophe Corvol
Steering committee
Clinical data
Sleep assessment
Genetic data
Brain MRI data
Stéphane Lehéricy
Simon Lewis
Elie Matar
Kaylena A. Ehgoetz Martens
Lachlan Churchill
Per Borghammer
Karoline Knudsen
Allan K. Hansen
Dario Arnaldi
Beatrice Orso
Pietro Mattioli
Luca Roccatagliata
Shady Rahayel