TY - JOUR
T1 - Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease
AU - Semba, Richard D.
AU - Moghekar, Abhay R.
AU - Hu, Jason
AU - Sun, Kai
AU - Turner, Randi
AU - Ferrucci, Luigi
AU - O'Brien, Richard
N1 - Funding Information:
This work was supported by National Institutes of Health grants R01 AG027012 , R01 HL111271 , R01 HL094507 , P50 AG05146 , U01 AG033655 , and the Burroughs Wellcome Trust for Translational Research .
PY - 2014/1/13
Y1 - 2014/1/13
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer's disease
KW - Brain
KW - Cerebrospinal fluid
KW - Klotho
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U2 - 10.1016/j.neulet.2013.10.058
DO - 10.1016/j.neulet.2013.10.058
M3 - Article
C2 - 24211693
AN - SCOPUS:84888403692
SN - 0304-3940
VL - 558
SP - 37
EP - 40
JO - Neuroscience Letters
JF - Neuroscience Letters
ER -