Driscoll, I; Ma, Y; Gallagher, CL; Johnson, SC; Asthana, S; Hermann, BP; Sager, MA; ... Okonkwo, OC; + view all Driscoll, I; Ma, Y; Gallagher, CL; Johnson, SC; Asthana, S; Hermann, BP; Sager, MA; Blennow, K; Zetterberg, H; Carlsson, CM; Engelman, CD; Dubal, DB; Okonkwo, OC; - view fewer (2021) Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes. Journal of Alzheimer's Disease , 79 (3) pp. 1297-1305. 10.3233/JAD-200944.

Preview

Text Zetterberg_Driscoll.pdf - Accepted Version Download (482kB) | Preview

Abstract

Background: Identification of new genetic variants that modify Alzheimer’s disease (AD) risk will elucidate novel targets for curbing the disease progression or delaying symptom onset. Objective: To examine whether the functionally advantageous KLOTHO gene KL-VS variant attenuates age-related alteration in cerebrospinal fluid (CSF) biomarkers or cognitive function in middle-aged and older adults enriched for AD risk. Methods: Sample included non-demented adults (N = 225, mean age = 63±8, 68% women) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center who were genotyped for KL-VS, underwent CSF sampling and had neuropsychological testing data available proximal to CSF draw. Covariate-adjusted multivariate regression examined relationships between age group (Younger versus Older; mean split at 63 years), AD biomarkers, and neuropsychological performance tapping memory and executive function, and whether these relationships differed between KL-VS non-carriers (KL-VSNC) and heterozygote (KL-VSHET). Results: In the pooled analyses, older age was associated with higher levels of total tau (tTau), phosphorylated tau (pTau), and their respective ratios to amyloid-β (Aβ)42 (ps ≤ 0.002), and with poorer performance on neuropsychological tests (ps ≤ 0.001). In the stratified analyses, KL-VSNC exhibited this age-related pattern of associations with CSF biomarkers (all ps ≤ 0.001), and memory and executive function (ps ≤ 0.003), which were attenuated in KL-VSHET (ps ≥ 0.14). Conclusion: Worse memory and executive function, and higher tau burden with age were attenuated in carriers of a functionally advantageous KLOTHO variant. KL-VS heterozygosity seems to be protective against age-related cognitive and biomolecular alterations that confer risk for AD.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item