Circulating Klotho Is Higher in Cerebrospinal Fluid than Serum and Elevated Among KLOTHO Heterozygotes in a Cohort with Risk for Alzheimer’s Disease
| Autor: | Gaitán, Julian M., Asthana, Sanjay, Carlsson, Cynthia M., Engelman, Corinne D., Johnson, Sterling C., Sager, Mark A., Wang, Dan, Dubal, Dena B., Okonkwo, Ozioma C. |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Heterozygote Aging Clinical Sciences Article Klotho cerebrospinal fluid Alzheimer Disease Genetics Acquired Cognitive Impairment Humans Glucuronidase Neurology & Neurosurgery Prevention General Neuroscience Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Neurodegenerative Diseases General Medicine Alzheimer's disease Hormones Brain Disorders Psychiatry and Mental health Clinical Psychology KL-VS Neurological Female Cognitive Sciences Geriatrics and Gerontology Alzheimer’s disease serum |
| Zdroj: | Journal of Alzheimer's disease : JAD, vol 90, iss 4 J Alzheimers Dis |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background: Klotho is a longevity and neuroprotective hormone encoded by the KLOTHO gene, and heterozygosity for the KL-VS variant confers a protective effect against neurodegenerative disease. Objective: Test whether klotho concentrations in serum or cerebrospinal fluid (CSF) vary as a function of KLOTHO KL-VS genotype, determine whether circulating klotho concentrations from serum and CSF differ from one another, and evaluate whether klotho levels are associated with Alzheimer’s disease risk factors. Methods: Circulating klotho was measured in serum (n = 1,116) and CSF (n = 183) of cognitively intact participants (aged 62.4 ± 6.5 years; 69.5% female). KLOTHO KL-VS zygosity (non-carrier; heterozygote; homozygote) was also determined. Linear regression was used to test whether klotho hormone concentration varied as a function of KL-VS genotype, specimen source, and demographic and clinical characteristics. Results: Serum and CSF klotho were higher in KL-VS carriers than non-carriers. Klotho concentration was higher in CSF than in serum. Females had higher serum and CSF klotho, while younger age was associated with higher klotho in CSF. Conclusion: In a cohort enriched for risk for Alzheimer’s disease, heterozygotic and homozygotic carriers of the KL-VS allele, females, and younger individuals have higher circulating klotho. Fluid source, KL-VS genotype, age, and sex should be considered in analyses of circulating klotho on brain health. |
| Databáze: | OpenAIRE |
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