, Volume 111, Issue 5, pp 591-601

Platelet phospholipase A2 activity in Alzheimer’s disease and mild cognitive impairment

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Summary.

Phospholipase A2 (PLA2) controls the metabolism of phospholipids in cell membranes. In the brain, PLA2 influences the processing of the amyloid precursor protein (APP) and thus the production of the amyloid-beta peptides (Aβ), which are the major components of the senile plaques in Alzheimer’s disease (AD). Reduced PLA2 activity has been reported in brain and in platelets of AD patients. In the present study we investigated PLA2 activity in platelets from 21 AD patients as compared to 17 healthy elderly controls and 11 individuals with mild cognitive impairment (MCI). Subjects were cognitively assessed by the Mini-Mental State Examination (MMSE) and the CAMDEX schedule. Platelet PLA2 activity was determined by radio-enzymatic assay, which mainly detected a calcium-independent form of the enzyme present also in the brain (iPLA2). PLA2 activity was significantly lower in AD than in controls (p < 0.001). Mean PLA2 activity in MCI individuals was between the values of AD patients and controls, with a subgroup showing PLA as low as the lowest AD patients, but the differences from MCI were not significant from AD and control groups. Lower PLA2 activity was significantly correlated with a worse cognitive performance both at the MMSE (p = 0.001) and the cognitive sub-scale of the CAMDEX inventory (p = 0.002). Our data replicate previous findings of reduced platelet PLA2 activity in AD. Both reduced PLA2 activity and the correlation with impaired cognition were also reported in brain tissue of AD patients, suggesting thus that the present determinations in platelets may be related to a reduction in the brain. In the brain the inhibition of PLA2 inhibits the physiological secretion of the APP, a mechanism that increases Aβ formation. Further longitudinal studies should investigate whether those MCI individuals with the lowest PLA2 values in platelets would be at a higher risk to develop AD during a longitudinal follow up.