Decreased phospholipase A₂ activity in the brain and in platelets of patients with Alzheimer's disease

Abstract

Phospholipase A₂ (PLA₂) is a key enzyme in the metabolism of membrane phospholipids. PLA₂ influences the processing and secretion of the amyloid precursor protein, which give rise to the β-amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). We investigated the PLA₂ activity in two samples: in post-mortem brains from 23 patients with AD and 20 non-demented elderly controls, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In AD brains PLA₂ activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA₂ activity correlated significantly with an earlier onset of the disease, an earlier age at death and higher counts of neurofibrillary tangles and senile plaques. In platelets PLA₂ activity was also significantly reduced in the AD group as compared with healthy and depressed controls. The reduction of the enzyme activity in platelets correlated with an early disease onset and with the severity of cognitive impairment, indicating a relationship between abnormally low PLA₂ 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 PLA₂ activity may contribute to the production of amyloidogenic peptides in the disease. Further studies are needed to examine whether PLA₂ activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.