Sex-related differences in genetically determined Alzheimer's disease
del Hoyo Soriano, Laura (Institut de Recerca Sant Pau)
Wagemann, O. (Ludwig-Maximilians-Universität (LMU) München)
Bejanin, Alexandre (Institut de Recerca Sant Pau)
Levin, J. (Munich Cluster for Systems Neurology (SyNergy))
Fortea, Juan (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Data:	2025
Resum:	We reviewed the literature on sex differences in genetically determined Alzheimer's disease (AD), focusing on autosomal dominant AD (ADAD), Down syndrome-associated AD (DSAD), and APOE4 homozygosity, particularly regarding disease penetrance, symptom onset and clinical progression, and trajectories for markers of amyloidosis (A), tau pathology (T) and neurodegeneration (N). Data suggests that sex differences in disease penetrance, symptom onset, and AT(N) biomarker trajectories are typically subtle for genetically determined AD populations. Noteworthy exceptions, such as increased neurodegeneration in later stages of the disease in females while similar cognitive outcomes, suggest a potential differential cognitive reserve that warrants further investigation. Additionally, the interaction between APOE genotype and sex reveals complex and multifaceted effects in DSAD, with potential implications for ADAD that remain underexplored. The smaller sex differences observed compared to sporadic AD offer insights into the different underlying disease mechanisms in genetically determined AD populations. Future research should prioritize sex-specific investigations in genetically determined AD, focusing on refining methodologies. This includes prioritizing longitudinal designs, adjustment for key confounders, and adherence to sex-specific guidelines.
Ajuts:	European Commission 2326 -GRT-2024A European Commission AARG-22-923680 European Commission H2020-SC1-BHC-2018-2020
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Matèria:	AT(N) biomarker trajectories in Alzheimer's disease (amyloid, tau and neurodegeneration biomarkers) ; Apolipoprotein E epsilon 4 (APOE4) homozygosity ; Autosomal dominant Alzheimer's disease (ADAD) ; Disease penetrance in Alzheimer's disease ; Down syndrome-associated Alzheimer's disease (DS-AD) ; Genetically determined Alzheimer's disease ; Sex differences in Alzheimer's disease ; Symptom onset in Alzheimer's disease
Publicat a:	Frontiers in aging neuroscience, Vol. 17 (2025) , p. 1522434, ISSN 1663-4365

DOI: 10.3389/fnagi.2025.1522434
PMID: 40103931

14 p, 4.0 MB

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