Plasma phosphorylated tau at threonine 181 (p-tau181) could be an Alzheimer disease (AD)-specific biomarker which may effectively monitor disease progression. These findings, from a longitudinal cohort study, were published in JAMA Neurology.

The AD Neuroimaging Initiative (ADNI) database was analyzed for this study. Patients with AD who were cognitively unimpaired (CU; n=378) were compared with those who were cognitively impaired (CImp; n=735). Patients underwent magnetic resonance imaging, positron emission tomography, and were assessed for blood biomarkers.

Patients were aged mean 74.0 (standard deviation [SD], 7.6) years, 53.9% were men, and 89.1% were White. The CImp cohort included patients with mild impairment (73.1%) and AD dementia (26.9%).

Faster longitudinal progression of hypometabolism and atrophy (r, -0.28; P <.001) and gray matter volume change (r, -0.28; P <.001) was associated, among CImp patients with higher p-tau181. Among CU patients, higher p-tau181 associated with future atrophy (r, -0.11; P =.03).


Continue Reading

Compared with the biomarker neurofilament light chain (NfL), plasma p-tau181 was more strongly associated with atrophy progression among the CImp cohort (bp-tau181 – bNfL, -0.13; 95% CI, -0.27 to 0.00). NfL associated with cognitive decline among the CImp cohort (r, 0.26; P <.001) and p-tau181 associated among both cohorts (CU: r, -0.12; P =.04; CImp: r, 0.35; P <.001).

Neurodegeneration caused by progressive decrease of glucose metabolism and increased atrophy were associated with the CImp cohort (r, -0.27; P <.001) and with a change in gray matter volume among both the CImp (r, -0.31; P <.001) and CU (r, -0.19; P <.001) cohorts. Longitudinal changes in plasma p-tau181 associated with prospective cognitive decline (CImp: r, 0.34; P <.001; CU: r, -0.24; P <.001).

Stratified by Ab status, plasma p-tau181 was associated with AD-typical regional neurodegeneration among Ab+ CImp (r, -0.27; P <.001) and with cognitive decline among patients who were Ab+ CImp (r, 0.31; P <.001) and Ab+ CU (r, -0.30; P =.003). Plasma p-tau181 was not associated with cognitive decline among Ab- patients (CImp: r, -0.01; P =.92; CU: r, -0.14; P =.05).

This study may have been biased as some patients were assessed for blood biomarkers and by brain scans at differing time periods.

These findings indicated baseline and longitudinal plasma p-tau181 may be indicative of AD-specific progressive neurodegeneration and cognitive decline, warranting additional study.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Moscoso A, Grothe MJ, Ashton NJ, et al. Longitudinal associations of blood phosphorylated tau181 and neurofilament light chain with neurodegeneration in Alzheimer disease. JAMA Neurol. 2021;e204986. doi:10.1001/jamaneurol.2020.4986