Sex differences in the association of Alzheimer's disease biomarkers and cognition in a multicenter memory clinic study

被引：0
作者：
Boccalini, Cecilia [1 ]
Peretti, Debora Elisa [1 ]
Scheffler, Max [2 ]
Mu, Linjing [3 ]
Griffa, Alessandra [4 ,5 ,6 ]
Testart, Nathalie [7 ]
Allali, Gilles [4 ,5 ]
Prior, John O. [7 ]
Ashton, Nicholas J. [8 ,9 ,10 ,11 ,12 ]
Zetterberg, Henrik [11 ,12 ,13 ,14 ,15 ,16 ,17 ]
Blennow, Kaj [9 ,15 ,18 ,19 ,20 ]
Frisoni, Giovanni B. [21 ]
Garibotto, Valentina [1 ,22 ,23 ]
机构：
[1] Univ Geneva, Geneva Univ, Fac Med, Lab Neuroimaging & Innovat Mol Tracers NIMTlab,Neu, Rue Gabrielle Perret Gentil 4, Geneva, Switzerland
[2] Geneva Univ Hosp, Div Neuroradiol, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland
[3] Swiss Fed Inst Technol, Inst Pharmaceut Sci, Vladimir Prelog Weg 1-5-10, CH-8093 Zurich, Switzerland
[4] Lausanne Univ Hosp, Leenaards Memory Ctr, Dept Clin Neurosci, Chem Mont Paisible 16, CH-1011 Lausanne, Switzerland
[5] Univ Lausanne, Chem Mont Paisible 16, CH-1011 Lausanne, Switzerland
[6] Ecole Polytech Fed Lausanne EPFL, Neuro X Inst, Med Image Proc Lab, Campus Biotech H4,Chemin Mines 9, CH-1202 Geneva, Switzerland
[7] Lausanne Univ Hosp, Dept Nucl Med & Mol Imaging, Rue Bugnon 46, CH-1011 Lausanne, Switzerland
[8] Stavanger Univ Hosp, Ctr Age Related Med, Armauer Hansens Vei 30, NO-4011 Stavanger, Norway
[9] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Wallinsgatan 6, S-43141 Molndal, Sweden
[10] Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Clin Neurosci Inst, London SE5 9RX, England
[11] South London & Maudsley NHS Fdn, UK NIHR Biomed Res Ctr Mental Hlth, London SE5 8AF, England
[12] South London & Maudsley NHS Fdn, Biomed Res Unit Dementia, London SE5 8AF, England
[13] UCL, UK Dementia Res Inst, London WC1E 6BT, England
[14] UCL, Inst Neurol, UK Dept Neurodegenerat Dis, London WC1N 3BG, England
[15] Univ Gothenburg, Clin Neurochem Lab, Sahlgrenska Acad, SU Molndals Sjukhus, SE-43180 Molndal, Sweden
[16] Hong Kong Ctr Neurodegenerat Dis, Clear Water Bay,Hong Kong Units 1501-1502,1512-151, Hong Kong, Peoples R China
[17] Univ Wisconsin Madison, Wisconsin Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI 53792 USA
[18] Sorbonne Univ, Pitie Salpetriere Hosp, Paris Brain Inst, ICM, Bd Hop 47, F-75013 Paris, France
[19] Univ Sci & Technol China, Inst Aging & Brain Disorders, Neurodegenerat Disorder Res Ctr, Dept Neurol,Div Life Sci & Med, Hefei 230001, Peoples R China
[20] USTC, Affiliated Hosp 1, Hefei 230001, Peoples R China
[21] Univ Hosp Geneva, Ctr Oncol, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland
[22] Geneva Univ Hosp, Div Nucl Med & Mol Imaging, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland
[23] Ecole Polytech Fed Lausanne, CIBM Ctr Biomed Imaging, AVP CP, CIBM Stn 6, Stn 6, CH-1015 Lausanne, Switzerland
来源：
ALZHEIMERS RESEARCH & THERAPY | 2025年 / 17卷 / 01期
关键词：
Sex; Neuroimaging; Alzheimer's disease; Biomarkers; tau-PET; Women; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; TAU; PET; IMPAIRMENT; RECOMMENDATIONS; WORKGROUPS; DEMENTIA; MRI;
D O I：
10.1186/s13195-025-01684-z
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Background This study investigated sex differences in the associations between Alzheimer's disease (AD) biomarkers, cognitive performance, and decline in memory clinic settings. Methods 249 participants (females/males:123/126), who underwent tau-PET, amyloid-PET, structural MRI, and plasma glial fibrillary acidic protein (GFAP) measurement were included from Geneva and Lausanne Memory Clinics. Mann-Whitney U tests investigated sex differences in clinical and biomarker data. Linear regression models estimated the moderating effect of sex on the relationship between biomarkers and cognitive performance and decline. Sex differences in cognitive decline were further evaluated using longitudinal linear mixed-effect models with three-way interaction effects. Results Women and men present similar clinical features, amyloid, and neurodegeneration. Women had higher tau load and plasma levels of GFAP than men (p < 0.05). Tau associations with amyloid (standardized beta = 0.54,p < 0.001), neurodegeneration (standardized beta=-0.44,p < 0.001), and cognition (standardized beta=-0.48,p < 0.001) were moderated by a significant interaction with sex. Specifically, the association between amyloid and tau was stronger among women than men (standardized beta=-0.19,p = 0.047), whereas the associations between tau and cognition and between tau and neurodegeneration were stronger among men than in women (standardized beta=-0.76,p = 0.001 and standardized beta=-0.56,p = 0.044). Women exhibited faster cognitive decline than men in the presence of severe cortical thinning (p < 0.001). Conclusion Women showed higher tau load and stronger association between amyloid and tau than men. In individuals with high tau burden, men exhibited greater neurodegeneration and cognitive impairment than women. These findings support that sex differences may impact tau deposition through an upstream interplay with amyloid, leading to downstream effects on neurodegeneration and cognitive outcomes.
引用
收藏
页数：11
相关论文
共 51 条
[1]  
Alzheimer’s disease facts and figures [published online ahead of print, 2020 Mar 10], Alzheimers Dement, (2020)
[2]  
Snyder H.M., Asthana S., Bain L., Brinton R., Craft S., Dubal D.B., Et al., Sex biology contributions to vulnerability to Alzheimer’s disease: a think tank convened by the women’s Alzheimer’s Research Initiative, Alzheimer’s Dement, 12, pp. 1186-1196, (2016)
[3]  
Lopez-lee C., Torres E.R.S., Carling G., Gan L., Mechanisms of sex differences in Alzheimer ’ s disease, Neuron
[4]  
Jack C.R., Bennett D.A., Blennow K., Carrillo M.C., Dunn B., Haeberlein S.B., Et al., NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease, Alzheimer’s Dement, 14, pp. 535-562, (2018)
[5]  
Hampel H., Cummings J., Blennow K., Gao P., Jack C.R., Vergallo A., Developing the ATX(N) classification for use across the Alzheimer disease continuum, Nat Rev Neurol, 17, pp. 580-589, (2021)
[6]  
Jr C.R.J., Andrews J.S., Beach T.G., Dunn B., Graf A., Hansson O., Et al., Revised criteria for diagnosis and staging of Alzheimer ’ s disease, Alzheimer ’ s Association Workgr, pp. 1-27, (2024)
[7]  
Ferretti M.T., Iulita M.F., Cavedo E., Chiesa P.A., Dimech A.S., Chadha A.S., Et al., Sex differences in Alzheimer disease — the gateway to precision medicine, Nat Rev Neurol, 14, pp. 457-469, (2018)
[8]  
Barnes L.L., Wilson R.S., Bienias J.L., Schneider J.A., Evans D.A., Bennett D.A., Sex differences in the clinical manifestations of Alzheimer disease pathology, Arch Gen Psychiatry, 62, pp. 685-691, (2005)
[9]  
Buckley R.F., Mormino E.C., Rabin J.S., Hohman T.J., Landau S., Hanseeuw B.J., Et al., Sex differences in the Association of Global Amyloid and Regional Tau Deposition measured by Positron Emission Tomography in clinically normal older adults, JAMA Neurol, 76, pp. 542-551, (2019)
[10]  
Buckley R.F., Scott M.R., Jacobs H.I.L., Schultz A.P., Properzi M.J., Amariglio R.E., Et al., Sex mediates relationships between Regional Tau Pathology and Cognitive decline, Ann Neurol, 88, pp. 921-932, (2020)
123456