Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease

- The “anti-aging hormone” klotho has been implicated in aging of the brain and cognition.
- Klotho levels are lower in cerebrospinal fluid in Alzheimer's disease compared with controls.
- Klotho levels are lower in cerebrospinal fluid of older compared with younger adults.
- There is no apparent circadian pattern to klotho levels in cerebrospinal fluid.

The aging-suppressor gene klotho encodes a single-pass transmembrane protein that is predominantly secreted by the choroid plexus of the brain and in the kidney. Klotho-deficient mice develop multiple aging phenotypes, including impaired cognition. Klotho concentrations have not been described in the CSF of humans. We measured klotho in the CSF of 20 older adults with Alzheimer's disease and in 20 older and 20 younger adults with normal cognition. In 10 adults, aged 38-87 years, CSF klotho measurements were made at baseline and every 6 h up to 18-30 h later. Mean (95% confidence interval [C.I.]) CSF klotho in men versus women were 899 (814, 983) and 716 (632, 801) pg/mL, respectively (P = 0.002). Mean (95% C.I.) CSF klotho in older adults with and without Alzheimer's disease were 664 (603, 725) and 776 (705, 828) pg/mL, respectively (P = 0.02), adjusting for sex. Mean (95% C.I.) klotho in older versus younger adults were 766 (658, 874) and 992 (884, 1100) pg/mL, respectively (P = 0.005), adjusting for sex. In the longitudinal study of CSF klotho, no significant circadian fluctuations were found in CSF klotho levels. This study suggests that CSF klotho concentrations are lower in females compared with males, in Alzheimer's disease, and in older versus younger adults.