Journal
NATURE REVIEWS NEUROLOGY
Volume 14, Issue 8, Pages 457-469Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41582-018-0032-9
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Funding
- AXA Research Fund
- Fondation Partenariale Sorbonne Universite
- Fondation pour la Recherche sur Alzheimer, Paris, France
- programme 'Investissements d'avenir' [ANR-10-IAIHU-06]
- Colam Initiatives
- programme 'PHOENIX'
- Fondation pour la Recherche sur Alzheimer
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- Canadian Foundation for Innovation
- Fonds de Recherche du Quebec-Sante
- Synapsis Foundation-Alzheimer Research Switzerland (ARS)
- Herbert H. Jasper Postdoctoral Research Fellowship from the Groupe de Recherche sur le Systeme Nerveux Central (GRSNC), Universite de Montreal
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Alzheimer disease (AD) is characterized by wide heterogeneity in cognitive and behavioural syndromes, risk factors and pathophysiological mechanisms. Addressing this phenotypic variation will be crucial for the development of precise and effective therapeutics in AD. Sex-related differences in neural anatomy and function are starting to emerge, and sex might constitute an important factor for AD patient stratification and personalized treatment. Although the effects of sex on AD epidemiology are currently the subject of intense investigation, the notion of sex-specific clinicopathological AD phenotypes is largely unexplored. In this Review, we critically discuss the evidence for sex-related differences in AD symptomatology, progression, biomarkers, risk factor profiles and treatment. The cumulative evidence reviewed indicates sex-specific patterns of disease manifestation as well as sex differences in the rates of cognitive decline and brain atrophy, suggesting that sex is a crucial variable in disease heterogeneity. We discuss critical challenges and knowledge gaps in our current understanding. Elucidating sex differences in disease phenotypes will be instrumental in the development of a 'precision medicine' approach in AD, encompassing individual, multimodal, biomarker-driven and sex-sensitive strategies for prevention, detection, drug development and treatment.
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