Many countries have validated the correlation between AD/CKD and Klotho levels. Comprehensive, multinational human
cohort studies have demonstrated a definitive link between AD/CKD and Klotho levels.

Association with Aging

Klotho's expression decreases with age.
Several cohort studies have confirmed that blood klotho levels decrease in proportion to age.

Reference

(2022) Espuch-Oliver A, Vázquez-LorenteH, Jurado-FasoliL, et al. References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18-85 Years. J Clin Med. 11(9):2415. Published 2022 Apr 25. doi:10.3390/jcm11092415

Klotho protein levels correlate with AD

Klotho protein levels correlate with AD: Human cohort studies strongly support the crucial protective role of klotho in AD development. CSF Klotho protein is lower in patients with Alzheimer's disease than in normal individuals. CSF Klotho protein is much lower in patients with severe AD than mild AD. A 2022 US cohort study (Oregon) confirmed the correlation between cerebrospinal fluid klotho proteins and serum klotho proteins

• CSF and blood klotho concentrations are highly correlated with the progression of Alzheimer's disease.

Reference

Semba RD, Moghekar AR, Hu J, et al. Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease. Neurosci Lett. 2014;558:37-40. doi:10.1016/j.neulet.2013.10.058

• Strong correlation between CSF Klotho protein levels blood Klotho levels.

Reference

Kundu P, Zimmerman B, Quinn JF, et al. Serum Levels of α-Klotho Are Correlated with Cerebrospinal Fluid Levels and Predict Measures of Cognitive Function. J Alzheimers Dis. 2022;86(3):1471-1481. doi:10.3233/JAD-215719

• Severe AD patients exhibit reduced levels of Klotho protein in their CSF.

Reference

Grøntvedt GR, Sando SB, Lauridsen C, et al. Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden. JAMA Netw Open. 2022;5(11):e2243232. Published 2022 Nov 1. doi:10.1001/jamanetworkopen.2022.43232

Klotho protein levels correlate with CKD

Human cohort studies demonstrate an inverse relationship between klotho protein levels and the progression of chronic kidney disease (CKD). Patients with CKD who have lower serum klotho protein levels exhibit higher mortality rates. Lower serum klotho protein levels are associated with more severe CKD. Lower serum klotho protein levels are associated with decreased glomerular filtration rate and reduced kidney survival.

• Reduced Klotho protein levels lead to an increased risk of CKD

Reference

Semba RD, Moghekar AR, Hu J, et al. Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease. Neurosci Lett. 2014;558:37-40. doi:10.1016/j.neulet.2013.10.058

• Strong correlation between CSF Klotho protein levels blood Klotho levels.

Reference

Kim HR, Nam BY, Kim DW, et al. Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis. 2013;61(6):899-909. doi:10.1053/j.ajkd.2013.01.024

• Severe AD patients exhibit reduced levels of Klotho protein in their CSF.

Reference

Grøntvedt GR, Sando SB, Lauridsen C, et al. Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden. JAMA Netw Open. 2022;5(11):e2243232. Published 2022 Nov 1. doi:10.1001
/jamanetworkopen.2022.43232