DECREASED PHOSPHOLIPASE A(2) ACTIVITY IN ALZHEIMER BRAINS

Phospholipase A(2) (PLA(2)) is a key-enzyme in the metabolism of membrane phospholipids. In cholinergic neurons PLA(2) controls the physico-chemical properties of neuronal membranes as well as the breakdown of phosphatidylcholine to produce choline for acetylcholine synthesis. Moreover PLA(2) influences the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). In the present study PLA(2) activity was investigated in post-mortem brains from 23 patients with AD and 20 nondemented elderly controls. In AD brains PLA(2) activity was significantly decreased in the parietal and to a lesser degree in the frontal cortex. Lower PLA(2) activity correlated significantly with an earlier onset of the disease, higher counts of neurofibrillary tangles and senile plaques and an earlier age at death, indicating a relationship between abnormally low PLA(2) activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA(2) activity may contribute to the cholinergic deficit and to the production of amyloidogenic peptides in the disease.