Disturbed Choline Plasmalogen and Phospholipid Fatty Acid Concentrations in Alzheimer's Disease Prefrontal Cortex

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by brain deposition of senile (neuritic) plaques containing β-amyloid, neurofibrillary tangles, synaptic loss, neuroinflammation, and overexpression of arachidonic acid (AA, 20:4n-6) metabolizing enzymes. Lipid concentration changes have been reported in different brain regions, but often partially and/or as a percent of the total concentration. In this study, we measured absolute concentrations (per gram wet weight) of a wide range of lipids in postmortem prefrontal cortex (Brodmann area 9) from 10 AD patients and 9 controls. Mean total brain lipid, phospholipid, cholesterol and triglyceride concentrations did not differ significantly between AD and controls. There was a significant 73% decrease in plasmalogen choline, but no difference in other measured phospholipids. Fatty acid concentrations in total phospholipid did not differ from control. However, docosahexaenoic acid (DHA, 22:6n-3) was reduced in ethanolamine glycerophospholipid and choline glycerophospholipid, but increased in phosphatidylinositol. AA was reduced in choline glycerophospholipid, but increased in phosphatidylinositol, while docosatetraenoic acid (22:4n-6), an AA elongation product, was reduced in total brain lipid, cholesteryl ester and triglyceride. These lipid changes may contribute to membrane instability and synaptic loss in AD, and reflect neuroinflammation and excitotoxicity.

Using direct infusion mass spectrometry for serum metabolomics in Alzheimer’s disease

“…Previously, low levels of ethanolamine plasmalogens have been reported in brain and serum from Alzheimer's disease patients [52,53], as well as decreased choline plasmalogens in brain [54]. Similarly, a decrease in plasmalogens is observed in our results, both in ethanolamine and choline plasmalogens ( Table 1).…”

The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

“…DHA has a number of pro-cell survival roles within cell membranes, including the production of anti-inflammatory D-series resolvins and neuroprotectins (Weylandt et al 2012). DHA is known to be severely reduced in many regions of the brain affected by AD pathology (Söderberg et al 1991;Martín et al 2010;Igarashi et al 2011;Cunnane et al 2012;Fabelo et al 2014); however, there are very few studies of this type looking specifically at the changes to the EC. Only a single study has examined the EC for changes in its phospholipids in AD, finding no changes in either total PC, PE or PS (Chan et al 2012).…”

Translational Research in Pediatrics IV: Solid Tissue Collection and Processing

“…• Proteins should be extracted from fresh or snap frozen material at -70°C or below 184,210,234 • Lipids should be extracted from fresh or snap frozen material at -20°C 108 or -80°C 223,287 Time to freeze • Freeze immediately after isolation. Samples derived postmortem should be frozen (at -80°C) short after death (maximum 2 h) for optimal results in protein studies and to avoid protein degradation 210,234 • Freeze immediately after isolation.…”

“…287 Different lipid subtypes can be successfully quantified by using mass spectrometric detection coupled with either gas, liquid, or thinlayer chromatography. 108,222,223,295 Tandem mass spectrometry with a lipid database 296 can be used to discriminate among chemical lipid variants with identical masses due to the identical number of acylic carbons and double bonds. 287 Matrix-assisted laser desorption/ ionization mass spectrometry permits the direct scanning of tissue slides, and it thus identifies the precise localization of different lipids in the tissue.…”