Elevated Activities of Lipases and Lysophospholipase in Alzheimer's Disease

Abstract

Two plasma membrane fractions were obtained from different regions of brains from patients with Alzheimer''s disease (AD) and normal aged individuals. One fraction was from synaptosomes (synaptosomal plasma membrane; SPM) and the other from glial cells and neuronal cell bodies (plasma membrane; PM). Among various regions analyzed, PM and SPM from the nucleus basalis of AD brains displayed 6- to 8-fold higher activities of mono- and diacylglycerol lipases than membranes from age-matched normal individuals. Membranes from the hippocampus region of AD brains also showed consistently higher activities of lipases than those from control brains. Similarly, the lysophospholipase activity in the cytosolic fraction of these regions also showed higher activity (4- to 6-fold) in AD than in corresponding fractions from normal human brains. The cause of increased activities of lipases and lysophospholipases in the nucleus basalis and hippocampus regions is not understood. However, marked elevations of acylhydrolases in the above regions may be due to overexpression, changes in levels of neuropeptides, intracellular calcium ions and/or lipid peroxides. All these are known to stimulate acylhydrolases. Autolytic changes which occur in the brain after death may markedly affect the activities of mono- and diacylglycerol lipases.

High throughput multiorgan metabolomics in the APP/PS1 mouse model of Alzheimer's disease

“…The accumulation of these lipids has been previously associated with accelerated hydrolysis of phosphatidylinositols by the action of phospholipase C in human AD serum . However, the main source for DAGs in tissues analyzed in this study could be an increased degradation of TAGs, in line with previous studies that suggest an association between different lipases and the risk for developing AD . Furthermore, cholesterol metabolism also was differentially impaired in the organs analyzed in this study.…”

Involvement of glutamate receptors, lipases, and phospholipases in long‐term potentiation and neurodegeneration

“…Because the NMDA receptor is linked to lipases and phospholipases (Sanfeliu et al, 1990), abnormalities in phospholipid metabolism are expected with AD. Indeed, we have observed a marked elevation of DAG and MAG lipase activities in neural membrane fractions prepared from nucleus basalis and hippocampal regions of 23 AD patients (Farooqui et al, 1990), and others have reported abnormal phospholipid metabolism in AD patients (Farooqui et al, 1988;Nitsch et al, 1992). A marked increase in PLC immunoreactivity is also found in the brains of AD patients (Shimohama et al, 1991).…”

Cytosolic phospholipase A2mediates neuronal apoptosis induced by soluble oligomers of the amyloid‐β peptide

“…Thus, it is crucial to better characterize the molecular mechanisms implicated in soluble Aβ peptide-induced cell death together with the physiological factors able to modulate the neurotoxicity of Aβ. In chronic neurodegenerative diseases such as AD, abnormal phospholipid metabolism (38,39) is accompanied by elevation in activities of both cPLA 2 (14) and other lipases (40). Indeed, changes in membrane phospholipids and high-energy phosphate metabolism occur before any clinical manifestation of AD and Aβ aggregation (41).…”