Associations between Plasma Biomarkers and Cognition in Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment: A Cross-Sectional and Longitudinal Study.

Tsai Tsai,Yang Yang,Chu Chu,Liang Liang,Lee Lee,Su Su,Lin Lin

doi:10.3390/jcm8111893

Abstract

Brain degeneration in patients with Alzheimer’s disease (AD) results from the accumulation of pathological amyloid-β (Aβ) plaques and tau protein tangles, leading to altered plasma levels of biomarkers. However, few studies have investigated the association between plasma biomarkers and cognitive impairment in patients with AD. In this cross-sectional study, we investigated correlations between mini-mental state examination (MMSE) scores and levels of plasma biomarkers in patients with amnestic mild cognitive impairment (aMCI) and AD. Thirteen individuals with normal cognition, 40 patients with aMCI, and 37 patients with AD were enrolled. Immunomagnetic reduction was used to assess the levels of plasma biomarkers, including amyloid Aβ1-40, Aβ1-42, total tau protein (t-Tau), and phosphorylated tau protein (threonine 181, p-Tau181). Our analysis revealed a significant negative correlation between MMSE and both measures of tau, and a trend toward negative correlation between MMSE and Aβ1-42. In a longitudinal study involving three patients with aMCI and two patients with AD, we observed strong negative correlations (r < −0.8) between changes in MMSE scores and plasma levels of t-Tau. Our results suggest that plasma levels of t-Tau and p-Tau181 can be used to assess the severity of cognitive impairment in patients with AD. Furthermore, the results of our preliminary longitudinal study suggest that levels of t-Tau can be used to monitor the progression of cognitive decline in patients with aMCI/AD.

Highlights

Patients with cognitive impairment exhibit decreased abilities across several cognitive domains, including attention, calculation, recall, language, orientation, and the ability to follow simple commands [1,2,3]
We examined the correlations between mini-mental state examination (MMSE) scores and plasma levels of these biomarkers in patients with amnestic mild cognitive impairment or Alzheimer’s disease (AD)
All plasma samples were detected within the limits of quantification of individual plasma biomarkers as assayed by immunomagnetic reduction (IMR) in the present study

Summary

Introduction

Patients with cognitive impairment exhibit decreased abilities across several cognitive domains, including attention, calculation, recall, language, orientation, and the ability to follow simple commands [1,2,3]. In Alzheimer’s disease (AD) patients, brain degeneration is believed to result from the accumulation of amyloid-β (Aβ) plaques and tau protein tangles in the brain [4,5,6]. Such accumulation leads to neuronal damage, and in turn to hippocampal atrophy, cortical thinning, and brain dysfunction [7,8,9]. Further studies confirmed opposite changes in Aβ1-42 levels in the plasma and CSF of AD patients [18,19,20] These results suggest that MMSE scores are associated with plasma levels of AD-related biomarkers

Methods

Results

Conclusion