Tik Muk, Asger Wretlind, Kourosh Hooshmand, Marc Clos-Garcia, Yue Liu, Anja Hviid Simonsen, Laura M Winchester, Tarunveer S Ahluwalia, Petroula Proitsi, Riccardo E Marioni, Thomas Kümler, Steen Gregers Hasselbalch, Cristina Legido-Quigley
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引用次数: 0
Abstract
Background: Alzheimer's disease (AD) disproportionately affects women, yet existing studies have been limited to single biofluids, individual hormones, or single dementia subtypes, leaving sex-stratified profiles across the cognitive impairment spectrum poorly defined. Here we address this gap by simultaneously quantifying nine steroid hormones spanning glucocorticoid (cortisol, 11-deoxycortisol), mineralocorticoid (aldosterone), progestogen (progesterone, 17-hydroxyprogesterone), androgen (testosterone, dihydrotestosterone), and estrogen (estradiol, estrone) pathways in paired CSF and plasma across five cognitive categories: no cognitive impairment, mild cognitive impairment (MCI) with AD pathology, MCI without AD pathology, AD dementia, and vascular dementia.
Methods: Steroid hormones were quantified by liquid chromatography-tandem mass spectrometry in paired cerebrospinal fluid (CSF) and plasma samples drawn from the same individuals from a cross-sectional study including 204 participants across five cognitive categories at the Danish Dementia Research Centre. Gender-stratified generalized linear models adjusted for age were applied. Cortisol findings were validated externally using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n = 426).
Results: Female participants with AD exhibited elevated CSF cortisol (fold change [FC] = 1.13; P = .04) and CSF 11-deoxycortisol (FC = 1.01; P = .03), alongside reduced plasma progesterone (FC = 0.90; P = .04). Male participants with AD showed elevated plasma aldosterone (FC = 1.19; P = 2.81e-03; q = 0.02). CSF cortisol correlated with amyloid-β42 and phosphorylated tau in female participants. ADNI validation confirmed elevated plasma cortisol in AD, with a larger effect in female participants.
Conclusions: Gender-dependent steroid hormone dysregulation in dementia highlights cortisol and aldosterone as potentially modifiable targets warranting further investigation.
期刊介绍：
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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