RELEVANZ DES METABOLISMUS DER MEMBRANPHOSPHOLIPIDE FUR DIE ALZHEIMER-DEMENZ

Translated title of the contribution: Alteration of the metabolism of membrane phospholipids in Alzheimer's disease

W. F. Gattaz, R. Levy, N. J. Cairns, H. Förstl, D. F. Braus, A. Maras

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

We found a decreased activity of the enzyme phospholipase A2 (PLA2) in brain tissue from 23 patients with Alzheimer's disease (AD) compared to 20 non-demented controls. The decrement was more pronounced in patients with an early onset of disease and correlated significantly with higher counts of senile plaques and neurofibrillary tangles. Decreased PLA2 activity may inhibit the secretion of the amyloid precursor protein (APP) and thus contribute to the formation of the β-amyloid peptide, the major component of the amyloid plaque in AD. Because PLA2 activity is under genetic control, it is conceivable that the enzyme activity in the brain is related to the activity in blood cells. To test this assumption we investigated PLA2 in platelet membranes from AD patients compared to healthy and psychiatric controls. Platelets are interesting peripheral models in AD research, because they contain and secrete APP. We determined the platelet PLA2 activity in 16 patients with a 'probable' AD (NINCDS-ADRDA criteria) as compared to 13 healthy controls and to 14 psychiatric patients with a major depression. There were no significant differences between the three groups regarding age and sex distribution. In the AD patients the cognitive performance was assessed with the CAMCOG and the Mini Mental State Exam (MMSE). The radioenzymatic assay for the determination of PLA2 activity is described elsewhere. Platelet PLA2 activity was significantly reduced in AD patients as compared to healthy (p < 0.03) and to psychiatric controls (p < 0.002). The reduction of the enzyme activity correlated with an early onset of the disease (r(s) = .43, p < 0,10) and with 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 PLA2 activity (11.8 ± 3.1) than patients with MMSE-score higher 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 decreased PLA2 activity was related to a more severe form of AD (early onset, more cognitive impairment and higher number of plaques and tangles). Moreover, reduced platelet PLA2 activity was specific for AD as compared to age-matched psychiatric controls. Further studies should clarify whether PLA2 activity in platelets could be useful as a peripheral marker for a subgroup of AD.

Translated title of the contributionAlteration of the metabolism of membrane phospholipids in Alzheimer's disease
Original languageGerman
Pages (from-to)8-12
Number of pages5
JournalFortschritte der Neurologie Psychiatrie
Volume64
Issue number1
DOIs
StatePublished - Jan 1996
Externally publishedYes

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