Platelet Total PLA 2 Activity,Serum Oxidative Level,and Plasma Cu/Zn Ratio: A Vicious Cycle with a Potential Role to Monitor MCI and Alzheimer's Disease Progression

Abstract

Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A₂ (PLA₂) are hydrolases with several functions in the brain, nevertheless their deregulation contributes to neurodegeneration. We evaluated platelet total PLA₂ activity (p_totPLA₂) in healthy elderly subjects (HE, n = 102), patients suffering from mild cognitive impairment (MCI, n = 90) and AD (n = 91). Platelets are considered “circulating neurons” and p_totPLA₂ appears to mirror the cerebral activity. p_totPLA₂ of the three cohorts was similar, but in MCI the higher p_totPLA₂ the worse the global cognitive status (Mini Mental State Examination score [MMSE]) and in AD the lower p_totPLA₂ the more severe the pathology stage (Clinical Dementia Rating [CDR]). Accordingly, MCI with MMSE ≥26 overlapped HE, in MCI with MMSE <26 and in AD with CDR 1 p_totPLA₂ increased, in AD with CDR 2 p_totPLA₂ decreased. In MCI p_totPLA₂ positively correlated with blood oxidation and inflammation, in AD it was the opposite. Finally, Discrimination Index (DI)—calculated multiplying p_totPLA₂, oxidative level and Cu/Zn ratio (an inflammation parameter)—differentiated MCI patients who progressed to dementia in the following 24 months and AD patients with the worse pathology development. Summarizing, p_totPLA₂ changes during MCI and AD progression, is linked, in opposite way, to oxidative/inflammatory status in MCI and AD and might help, when included in DI, to identify MCI converters to dementia and AD patients with the more severe prognosis. p_totPLA₂ may have a diagnostic/prognostic value and be a potential therapeutic target.