Decreased phospholipase A2 activity in cerebrospinal fluid of patients with dementia

Abstract

Phospholipase A2 (PLA2) is involved in important aspects of dementia, for example neurotransmission and memory processing, membrane function, choline availability, and antioxidative defense. Reduced PLA2-activity has been reported so far in blood samples and postmortem neuronal tissue in Alzheimer disease. For the first time, we studied PLA2 in cerebrospinal fluid (CSF) in Alzheimer disease (AD), vascular (VD), and mixed Alzheimer/vascular dementia (MD). Intracellular PLA2 was assessed in CSF of 16 AD, 12 VD, 15 MD patients, and 19 healthy control subjects. A fluorometric assay was applied using the PLA2-specific substrate NBDC6-HPC. Significantly reduced PLA2 activity was not only found in AD, but also in VD and MD. This finding was independent of demographic co-variates and medication. PLA2 results in CSF corroborate previous findings of impaired PLA2 function in Alzheimer's disease and extend these to patients with VD. They are likely to reflect an involvement of PLA2 impairment in a variety of pathomechanisms crucial in different dementia subtypes, in which disruption of cholinergic neurotransmission and disturbance of intact membrane function appear to be the key mechanisms.

Phospholipase A2 activity is associated with structural brain changes in schizophrenia

“…Intracellular acting (cytosolic) PLA 2 enzymes occur ubiquitary, are activated on demand, and are (as other serine esterases) able to pass the blood-brain barrier (Reiber, 2005). Once being activated, increased enzyme activity can be measured in blood serum and cerebrospinal fluid, and we have previously shown a close correlation of PLA 2 activity in serum and CSF (as obtained from lumbar puncture samples) in other patient cohorts (Smesny et al, 2008). The activity of PLA 2 measured in this study comprises cytosolic isoenzymes of groups (2) and (3).…”

Lipidomics of Alzheimer's disease: current status

“…Ca ++ -dependent PLA2 is increased in AD CSF [36], decreased in AD cortex [31], and unaffected in AD cerebellum [31]. Ca ++ -independent PLA2 is decreased in both AD CSF [37] and AD cortex [31], and unaffected in AD cerebellum [31]. Clearly, further characterization of changes in the multiple isoforms of PLA2 in AD is required.…”

Phospholipase A2activity in first episode schizophrenia: Associations with symptom severity and outcome at week 12

“…selective antibodies for in PLA 2 proteins in serum and in cerebrospinal fl uid (as obtained from lumbar puncture samples), and showed that the enzyme composition was identical ( Smesny et al 2008). Based on this result, we can assume that the fi ndings of this study relate closely to membrane lipid biochemistry within the CNS.…”