Plasma p-tau₁₈₁ shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau

Introduction We examined the ability of plasma hyperphosphorylated tau (p-tau)(181) to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL). Methods Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables. Results Plasma p-tau(181) discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau(181) had a direct association with cognitive diagnosis in a bootstrapped GGM. Discussion These results support plasma p-tau(181) for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.