Plasma p-Tau181 Outperforms Cerebrospinal Fluid Total Tau in Terms of Alzheimer’s Disease Diagnosis

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dementia, and is a serious concern for the health of individuals and government health care systems worldwide. Gray matter atrophy and white matter damage are major contributors to cognitive deficits experienced by patients with AD, as seen through magnetic resonance imaging (MRI). Many of these brain changes associated with AD begin to occur about 15 years before the onset of initial clinical symptoms. Therefore, it is critical to find biomarkers reflective of these brain changes associated with AD to identify this disease and monitor its prognosis and development. The level of hyperphosphorylated tau 181 (p-Tau181) in the plasma has been recently considered as a novel biomarker for the presence of AD, with increased levels in patients with AD, preclinical AD, and those experiencing mild cognitive impairment (MCI). In the current study, we examined the association of cerebrospinal fluid (CSF) and plasma levels of p-Tau181 with structural brain changes pertaining to cortical thickness, cortical volume, surface area, and subcortical volume in MCI patients. In this cross-sectional study we included the information of 461 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The results of voxel-wise partial correlation analyses showed a significant negative correlation between the increased levels of plasma p-Tau181, CSF total tau, and CSF p-Tau181 and structural changes in widespread brain regions. These results provide evidence for the use of plasma p-Tau181 as a diagnostic marker for structural changes in the brain associated with the early stages of AD and neurodegeneration.