DECREASED PHOSPHOLIPASE A(2) ACTIVITY IN THE BRAIN AND IN PLATELETS OF PATIENTS WITH ALZHEIMERS-DISEASE

Phospholipase A(2) (PLA(2)) is a key enzyme in the metabolism of membr ane phospholipids. PLA(2) influences the processing and secretion of t he amyloid precursor protein, which give rise to the beta-amyloid pept ide, the major component of the amyloid plaque in Alzheimer's disease (AD). We investigated the PLA(2) activity in two samples: in post-mort em brains from 23 patients with AD and 20 non-demented elderly control s, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In A D brains PLA(2) activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA(2) activity c orrelated significantly with an earlier onset of the disease, an earli er age at death and higher counts of neurofibrillary tangles and senil e plaques. In platelets PLA(2) 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, indicati ng a relationship between abnormally low PLA(2) activitiy and a more s evere form of the illness. The present results provide new evidence fo r a disordered phospholipid metabolism in AD brains and suggest that r educed PLA(2) activity may contribute to the production of amyloidogen ic peptides in the disease. Further studies are needed to examine whet her PLA(2) activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.