Neurobiology of Aging | May 4, 2021
Lord J, Zettergren A, Ashton NJ, Karikari TK, Benedet AL, Simrén J, Hye A, Aarsland D, Blennow K, Zetterberg H and Proitsi P
Neurobiol Aging. 2021
DOI: 10.1016/j.neurobiolaging.2021.04.018
Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer’s Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1153 participants from 2 independent cohorts. No loci, other than those within the APOE genomic region (lead variant = rs429358, beta = 0.32, p =8.44 × 10−25) demonstrated association with P-tau181 at genome-wide significance (p < 5 × 10−08), though rs60872856 on chromosome 2 came close (beta = -0.28, p = 3.23 × 10−07, nearest gene=CYTIP). As the APOE ε4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.
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