Decreased Levels of Blood AMPKα1 but not AMPKα2 Isoform in Patients with Mild Cognitive Impairment and Alzheimer's Disease: A Pilot Study

Background: There is an urgent need to develop feasible biomarkers for diagnosis and prognosis of Alzheimer's disease (AD). Mounting evidence implicates that dysregulation of energy metabolism is a key and early event in AD pathogenesis. AMP-activated protein kinase (AMPK) is a central molecular sensor that plays a critical role in maintaining cellular energy homeostasis, and aberrant brain AMPK activities are linked to AD pathophysiology. Objective: We aimed to investigated protein levels of AMPK alpha isoforms, AMPK alpha 1 and AMPK alpha 2, in plasma samples from patients clinically diagnosed with mild cognitive impairment (MCI) or AD, along with age-matched healthy controls. Methods: 30 participants (10 MCI, 10 AD, and 10 controls) were included in our pilot study. Plasma levels of AMPK alpha 1 and AMPK alpha 2 were determined by ELISA. Receiver operating characteristic (ROC) analysis was used to assess sensitivity and specificity. Linear regression was used to assess the correlation between levels of AMPK alpha isoforms and other biomarkers. Results: Plasma levels of AMPK alpha 1 were decreased in MCI and AD patients, while levels of AMPK alpha 2 were unaltered as compared to controls. ROC analysis showed relatively high sensitivity and specificity for AMPK alpha 1 to distinguish MCI and AD from controls. Linear regression analysis showed that plasma levels of AMPK alpha 1 were correlated with a brain imaging biomarker (AD signature cortical thicknesses). Conclusion: Plasma levels of AMPK alpha 1 were decreased in MCI and AD patients. Future endeavor to explore whether blood AMPK alpha 1 protein expression has the value as a potential biomarker for AD and MCI diagnosis shall be encouraged.