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Platelet biomarkers identifying mild cognitive impairment in type 2 diabetes patients

Haitao Yu1,2, Yanchao Liu1,3, Ting He1

  • 1Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aging Cell
|September 16, 2021
PubMed

Insights

Type 2 diabetes (T2DM) patients with cognitive decline show altered platelet proteins. Increased optineurin levels may help predict Alzheimer's disease (AD) risk in these individuals.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Endocrinology

Background:

  • Type 2 diabetes mellitus (T2DM) is a significant risk factor for Alzheimer's disease (AD).
  • Early identification of peripheral biomarkers for mild cognitive impairment (MCI) in T2DM patients is crucial for AD prediction.
  • Platelet proteomics offers a potential avenue for discovering such biomarkers.

Purpose of the Study:

  • To identify peripheral protein biomarkers in platelets associated with mild cognitive impairment (MCI) in patients with Type 2 diabetes mellitus (T2DM).
  • To investigate the correlation between specific platelet proteins and cognitive function, amyloid levels, and GSK-3β phosphorylation in T2DM patients.

Main Methods:

  • Platelet proteomic analysis was conducted on T2DM patients with (T2DM-MCI) and without (T2DM-nMCI) mild cognitive impairment.
  • Pearson correlation analysis was used to assess relationships between protein expression and cognitive scores (MMSE), Aβ1-42/Aβ1-40 ratio, and rGSK-3β(T/S9).
  • Machine learning models were employed to evaluate the diagnostic efficiency of identified biomarkers.

Main Results:

  • Mitophagy/autophagy, insulin signaling, and glycolysis/gluconeogenesis pathways were significantly implicated in T2DM-MCI.
  • Increased optineurin, an autophagy-related protein, correlated with reduced MMSE, elevated Aβ1-42/Aβ1-40, and increased rGSK-3β(T/S9).
  • Optineurin alone could distinguish T2DM-MCI from T2DM-nMCI; a combination with rGSK-3β(T/S9) achieved high diagnostic accuracy (AUC 0.927).

Conclusions:

  • Platelet optineurin is a promising biomarker for predicting cognitive decline in T2DM patients.
  • Combined analysis of platelet optineurin and rGSK-3β(T/S9) shows potential for early AD risk assessment in T2DM.
  • These findings highlight the role of autophagy and related pathways in the T2DM-associated cognitive impairment.
Keywords:
Alzheimer's diseasemild cognitive impairmentoptineurinperipheral biomarkersplateletproteomicstype 2 diabetes mellitus

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