Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia-related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex-specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non-disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex-specific AD susceptibility and potential footholds for sex-based interventions targeting these systems. We conclude by outlining immediate and long-term actions to address the intersection of NSSs, sex, and AD.
Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease / Rae, Rosaria J.; Alberhasky, Jessica Marie Hunter; Baillet, Marion; Bangasser, Debra A.; Belloy, Michael E.; Berry, Anne S.; Berteotti, Chiara; Bow, Hannah; Buckley, Rachel; Caldwell, Jessica Z. K.; Carpi, Matteo; Clark, Benjamin J.; Ciampa, Claire J.; Conley, Alexander C.; Dahl, Martin J.; Donaldson, Zoe R.; Ehrenberg, Alexander J.; Einstein, Gillian; Falgàs, Neus; Fenlon, Haley A.; Fitzhugh, Megan C.; Froemke, Robert C.; Gallay, Clara; Grinberg, Lea Tenenholz; Hamilton, Derek A.; Hasan, Zia; Huarte, Oihane Uriarte; Jabeen, Shaista; Jacobs, Heidi I. L.; Kolling, Louis John; Koops, Elouise A.; Lenzoni, Sabrina; Liguori, Claudio; Manca, Riccardo; Marcinkiewcz, Catherine A.; Omoluabi, Tamunotonye; Oria, Rademene; Orsini, Caitlin A.; Ortega, Nancy Elizabeth; Pa, Judy; Pentkowski, Nathan S.; Pereira, Joana B.; Ramos, Rhudovic; Sargin, Derya; Satpati, Abhijit; Selles, Maria Clara; Seto, Mabel; Shaik, Shabana M.; Sindi, Shireen; Son, Gowoon; Ucheagwu, Valentine; Van Egroo, Maxime; Yuan, Qi; Kelberman, Michael A.. - In: ALZHEIMER'S & DEMENTIA. - ISSN 1552-5260. - 22:3(2026). [10.1002/alz.71291]
Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease
Carpi, Matteo;
2026
Abstract
Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia-related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex-specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non-disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex-specific AD susceptibility and potential footholds for sex-based interventions targeting these systems. We conclude by outlining immediate and long-term actions to address the intersection of NSSs, sex, and AD.| File | Dimensione | Formato | |
|---|---|---|---|
|
Alzheimer s Dementia - 2026 - Rae - Sex differences in neuromodulatory subcortical systems and their implications for.pdf
accesso aperto
Note: Rae_Sex differences_2026
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
1.94 MB
Formato
Adobe PDF
|
1.94 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
