ALTERATION OF THE METABOLISM OF MEMBRANE PHOSPHOLIPIDS IN ALZHEIMERS-DISEASE

We found a decreased activity of the enzyme phospholipase A(2) (PLA(2) ) in brain tissue from 23 patients with Alzheimer's disease (AD) compa red to 20 non-demented controls. The decrement was more pronounced in patients with an early onset of disease and correlated significantly w ith higher counts of senile plaques and neurofibrillary tangles. Decre ased PLA(2) activity may inhibit the secretion of the amyloid precurso r protein (APP) and thus contribute to the formation of the beta-amylo id peptide, the major component of the amyloid plaque in AD. Because P LA(2) activity is under genetic control, it is conceivable that the en zyme activity in the brain is related to the activity in blood cells. To test this assumption we investigated PLA(2) in platelet membranes f rom AD patients compared to healthy and psychiatric controls. Platelet s are interesting peripheral models in AD research, because they conta in and secrete APP. We determined the platelet PLA(2) activity in 16 p atients with a ''probable'' AD (NINCDS-ADRDA criteria) as compared to 13 healthy controls and to 14 psychiatric patients with a major depres sion. There were no significant differences between the three groups r egarding age and sex distribution. In the AD patients the cognitive pe rformance was assessed with the CAMCOG and the Mini Mental State Exam (MMSE). The radioenzymatic assay for the determination of PLA(2) activ ity is described elsewhere. Platelet PLA(2) activity was significantly reduced in AD patients as compared to healthy (p < 0.03) and to psych iatric controls (p < 0.002). The reduction of the enzyme activity corr elated with an early onset of the disease (r(s) = .43, p < 0,10) and w ith the cognitive impairment in the CAMCOG (r(s) = .55, p < 0,05). AD patients with a MMSE-score lower than 10 (median) showed significantly lower PLA(2) activity (11.8 +/ 3.1) than patients with MMSE-score hig her than 10 (16.2 +/- 4.6, p < 0.05). These findings in platelets are in line with our previous results in brain tissue. In both studies dec reased PLA(2) activity was related to a more severe form of AD (early onset, more cognitive impairment and higher number of plaques and tang les). Moreover, reduced platelet PLA(2) activity was specific for AD a s compared to age-matched psychiatric controls. Further studies should clarify whether PLA(2) activity in platelets could be useful as a per ipheral marker for a subgroup of AD.