Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) are indicators of both amyloid and tau pathology in clinical settings, but their performance in heterogeneous community-based populations is unclear. We examined P-tau181 and P-tau217 (n = 1,329, aged 30–98 years), in the population-based Mayo Clinic Study of Aging. Continuous, unadjusted plasma P-tau181 and P-tau217 predicted abnormal amyloid positron-emission tomography (PET) (area under the receiver operating characteristic curve (AUROC) = 0.81–0.86) and tau PET entorhinal cortex (AUROC > 0.80), but was less predictive of a tau PET temporal region of interest (AUROC < 0.70). Multiple comorbidities were associated with higher plasma P-tau181 and P-tau217 levels; the difference between participants with and without chronic kidney disease (CKD) was similar to the difference between participants with and without elevated brain amyloid. The exclusion of participants with CKD and other comorbidities affected the establishment of a normal reference range and cutpoints. Understanding the effect of comorbidities on P-tau181 and P-tau217 levels is important for their future interpretation in the context of clinical screening, diagnosis or prognosis at the population level.

血浆磷酸化 tau 181 (P-tau181) 和 217 (P-tau217) 是临床环境中淀粉样蛋白和 tau 病理学的指标，但它们在异质社区人群中的表现尚不清楚。我们检查了 P-tau181 和 P-tau217 ( n = 1,329，年龄在 30-98 岁之间），在基于人群的 Mayo Clinic 老龄化研究中。连续、未调整的血浆 P-tau181 和 P-tau217 预测异常淀粉样蛋白正电子发射断层扫描 (PET)（接受者操作特征曲线下面积 (AUROC) = 0.81–0.86）和 tau PET 内嗅皮层 (AUROC > 0.80)，但对感兴趣的 tau PET 时间区域的预测性较低 (AUROC < 0.70)。多种合并症与较高的血浆 P-tau181 和 P-tau217 水平相关；患有和不患有慢性肾脏疾病 (CKD) 的参与者之间的差异类似于患有和未患有脑淀粉样蛋白升高的参与者之间的差异。排除患有 CKD 和其他合并症的参与者会影响正常参考范围和临界点的建立。