AUTHOR=Raber Jacob , Pederson Alexandra , Bunnell Emily , Mattek Nora , Gray Nora E. , Kohama Steven G. , Weiss Alison R. , Quinn Joseph F. , Urbanski Henryk F. 

TITLE=α-klotho as a biomarker of amyloid β levels in the cerebrospinal fluid

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 17 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1599402

DOI=10.3389/fnagi.2025.1599402

ISSN=1663-4365

ABSTRACT=IntroductionCSF α-klotho levels might affect Aβ40, Aβ42, and the Aβ42/40 ratio in the cerebrospinal fluid (CSF).MethodsCSF α-klotho was assayed in ovariectomized rhesus macaques (NHPs) maintained on a Western-style diet (WSD) to assess the effect of estrogen hormone therapy (HT). CSF and serum α-klotho was also analyzed in females and males of different ages and whether it was associated with Aβ42, Aβ40, or the Aβ42/40 ratio. Furthermore, CSF and serum α-klotho were analyzed in women and men with dementia and controls and whether they were associated with CSF Aβ levels.ResultsHT was associated with increased CSF α-klotho levels. Furthermore, α-klotho and Aβ levels were correlated in a species- and cognitive health-dependent fashion. Higher CSF and serum levels of α-klotho were seen in controls than in patients with dementia.DiscussionUnderstanding the species differences in the beneficial effects of α-klotho on CSF Aβ physiology should open new avenues for treating AD.