Changes in Plasma Amyloid and Tau in a Longitudinal Study of Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease

Background: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). Methods: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 AD patients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aβ) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. Results: Longitudinal data analysis showed an evolution of Aβ-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aβ42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. Conclusion: Plasma Aβ and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aβ concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers.