Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer's disease.
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 beta-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.
Gattaz
W F
WF
Central Institute of Mental Health, Mannheim, Germany.
Cairns
N J
NJ
Levy
R
R
Förstl
H
H
Braus
D F
DF
Maras
A
A
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D001792:Blood Platelets / Q000201:enzymology*; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D017397:Prefrontal Cortex / Q000473:pathology
D010741:Phospholipases A; D054467:Phospholipases A2