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

Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A(2) (PLA(2)) are hydrolases with several functions in the brain, nevertheless their deregulation contributes to neurodegeneration. We evaluated platelet total PLA(2) activity (p(tot)PLA(2)) 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(tot)PLA(2) appears to mirror the cerebral activity. p(tot)PLA(2) of the three cohorts was similar, but in MCI the higher p(tot)PLA(2) the worse the global cognitive status (Mini Mental State Examination score [MMSE]) and in AD the lower p(tot)PLA(2) 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(tot)PLA(2) increased, in AD with CDR 2 p(tot)PLA(2) decreased. In MCI p(tot)PLA(2) positively correlated with blood oxidation and inflammation, in AD it was the opposite. Finally, Discrimination Index (DI)-calculated multiplying p(tot)PLA(2), 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(tot)PLA(2) 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(tot)PLA(2) may have a diagnostic/prognostic value and be a potential therapeutic target.