Low platelet iPLA₂ activity predicts conversion from mild cognitive impairment to Alzheimer's disease: a 4-year follow-up study.

Reduced phospholipase A₂ (PLA₂) activity has been reported in the brain and in blood cells of patients with Alzheimer's disease (AD). Individuals with mild cognitive impairment (MCI) are at increased risk of developing AD. In the present study, we determined the activity of distinct PLA₂ subgroups (iPLA₂, sPLA₂ and cPLA₂) in older adults with MCI as compared to patients with mild dementia due to AD and to cognitively healthy controls. We investigated whether decreased PLA₂ activity at baseline is associated with the progression of MCI to AD upon follow-up during a period of 4 years. The activity of PLA₂ subgroups was determined in platelets from 169 elderly adults. Progression of MCI to AD was ascertained by standard clinical criteria for AD upon follow-up. At baseline, iPLA₂ activity was significantly decreased (p = 0.001) in patients with AD and MCI as compared to controls. Patients with MCI who progressed to AD during follow-up showed significantly lower iPLA₂ activity at baseline as compared to patients with MCI who did not progress to AD (p = 0.009). Moreover, subjects from the control group at baseline who progressed to MCI during follow-up had lower sPLA₂ and cPLA₂ (p = 0.014 and p = 0.009, respectively). Our findings suggest that low platelet iPLA₂ activity may be a risk marker for AD in subjects with MCI. Moreover, low sPLA₂ and cPLA₂ were related to cognitive decline in healthy controls, suggesting a relationship with the very early stages of the disease.