Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov 6;8(11):1893.
doi: 10.3390/jcm8111893.

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

Chia-Lin Tsai  1 , Chih-Sung Liang  2 , Jiunn-Tay Lee  1 , Ming-Wei Su  3 , Chun-Chieh Lin  1 , Hsuan-Te Chu  2 , Chia-Kuang Tsai  1 , Guan-Yu Lin  1 , Yu-Kai Lin  1 , Fu-Chi Yang  1
Affiliations

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

Chia-Lin Tsai et al. J Clin Med. .

Abstract

Brain degeneration in patients with Alzheimer's disease (AD) results from the accumulation of pathological amyloid- (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 A1-40, A1-42, 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 A1-42. 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.

Keywords: Alzheimer’s disease; amnestic mild cognitive impairment; immunomagnetic reduction; plasma biomarkers.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Individual and combined plasma biomarkers. Levels of (a) Aβ1-40, (b) Aβ1-42, (c) t-Tau (d) p-Tau181, (e) Aβ1-42/Aβ1-40, (f) Aβ1-42 × t-Tau, and (g) Aβ1-42 × p-Tau181 versus MMSE scores for the 90 participants (HCs, aMCI, and AD) in the cross-sectional analysis. Aβ: amyloid-β; MMSE: mini-mental state examination; HC: healthy control; aMCI: amnestic mild cognitive impairment; AD: Alzheimer’s disease; t-Tau: total tau; p-Tau181: phosphorylated tau 181.
Figure 2
Figure 2
Changes in individual and combined plasma biomarkers for two AD patients (■ and •) and three aMCI patients (○, □, and △). Levels of (a) Aβ1-40, (b) Aβ1-42, (c) t-Tau, (d) p-Tau181, (e) Aβ1-42/Aβ1-40, (f) Aβ1-42 × t-Tau, and (g) Aβ1-42 × p-Tau181 versus changes in MMSE scores for the five individual patients with aMCI (○, □, and △) or AD (■ and •) in the longitudinal analysis.
Figure 3
Figure 3
Relationship between plasma levels of p-Tau181 and t-Tau for all participants in the cross-sectional study.
See this image and copyright information in PMC

References

    1. Salmon D.P., Bondi M.W. Neuropsychological assessment of dementia. Annu. Rev. Psychol. 2009;60:257–282. doi: 10.1146/annurev.psych.57.102904.190024. - DOI - PMC - PubMed
    1. Chertkow H., Feldman H.H., Jacova C., Massoud F. Definitions of dementia and predementia states in Alzheimer’s disease and vascular cognitive impairment: Consensus from the Canadian conference on diagnosis of dementia. Alzheimer’s Res. Ther. 2013;5(Suppl. 1):S2. doi: 10.1186/alzrt198. - DOI - PMC - PubMed
    1. Knopman D.S., Petersen R.C. Mild cognitive impairment and mild dementia: A clinical perspective. Mayo Clin. Proc. 2014;89:1452–1459. doi: 10.1016/j.mayocp.2014.06.019. - DOI - PMC - PubMed
    1. Bartzokis G., Lu P.H., Mintz J. Human brain myelination and amyloid beta deposition in Alzheimer’s disease. Alzheimer’s Dement. 2007;3:122–125. doi: 10.1016/j.jalz.2007.01.019. - DOI - PMC - PubMed
    1. Alafuzoff I., Thal D.R., Arzberger T., Bogdanovic N., Al-Sarraj S., Bodi I., Bugiani O., Duyckaerts C., Gelpi E., Gentleman S., et al. Assessment of β-amyloid deposits in human brain: A study of the brain net Europe Consortium. Acta Neuropathol. 2009;117:309–320. doi: 10.1007/s00401-009-0485-4. - DOI - PMC - PubMed

LinkOut - more resources