Plasma phosphorylated tau at threonine 181 (p-Tau181) could be an Alzheimer’s-specific biomarker that can effectively monitor the progression of the disease. These results from a longitudinal cohort study were published in JAMA Neurology.
The database of the AD Neuroimaging Initiative (ADNI) was analyzed for this study. Patients with AD who were not cognitively impaired (CU; n = 378) were compared with those who were cognitively impaired (CImp; n = 735). The patients underwent magnetic resonance imaging and positron emission tomography and examined for blood biomarkers.
The patients had an average age of 74.0 years (standard deviation) [SD], 7.6) years, 53.9% were men and 89.1% were white. The CImp cohort included patients with mildly impaired (73.1%) and AD dementia (26.9%).
In CImp patients with a higher p-tau181, faster longitudinal progression of hypometabolism and atrophy (r, -0.28; P <0.001) and gray matter volume change (r, -0.28; P <0.001) were associated. In UC patients, a higher p-tau181 value was associated with future atrophy (r, -0.11; P = 0.03).
Compared to the biomarker neurofilament light chain (NfL), plasma p-tau181 was more strongly associated with progression of atrophy in the CImp cohort (bp-tau181 – bNfL, -0.13; 95% CI, -0.27 up to 0.00). NfL associated with cognitive decline in the CImp cohort (r, 0.26; P <0.001) and p-tau181 in both cohorts (CU: r, -0.12; P = 0.04; CImp: r, 0, 35; P <0.001)).
Neurodegeneration caused by progressive decline in glucose metabolism and increased atrophy was observed with the CImp cohort (r, -0.27; P <0.001) and with a change in gray matter volume in both CImp (r, -0, 31; P <0.001) associated) and CU (r, -0.19; P <0.001) cohorts. Longitudinal changes in plasma p-tau181 in connection with a prospective cognitive decline (CImp: r, 0.34; P <0.001; CU: r, -0.24; P <0.001).
Plasma p-tau181 was stratified by Ab status with an AD-typical regional neurodegeneration in Ab + CImp (r, -0.27; P <0.001) and with a cognitive decline in patients with Ab + CImp (r, 0, 31; P <0.001) associated) and Ab + CU (r, -0.30; P = 0.003). Plasma p-tau181 was not associated with a cognitive decline in Ab patients (CImp: r, -0.01; P = 0.92; CU: r, -0.14; P = 0.05).
This study may have been biased as some patients were screened for blood biomarkers and brain scans at different times.
These findings suggest that p and longitudinal plasma p-tau181 may indicate AD-specific progressive neurodegeneration and cognitive decline, warranting additional investigation.
Disclosure: Several authors have declared their affiliations with the industry. For a full list of the details, see the original article.
Moscoso A, Grothe MJ, Ashton NJ et al. Longitudinal associations of blood phosphorylated tau181 and light chain of neurofilaments with neurodegeneration in Alzheimer’s disease. JAMA Neurol. 2021; e204986. doi: 10.1001 / jamaneurol.2020.4986
This article originally appeared on Psychiatry Advisor