Epidermal fatty acid binding protein (FABP5) and brain fatty acid binding protein STI571 (FABP7), both present in the brain, remain to be evaluated. Circulating plasmalogens and plasmalogen precursors also gain access to the CNS. Circulating plasmalogens are synthesized mainly by the liver and gastrointestinal epithelium [14,19] and are exported into the circulation via chaperone transport proteins of which low density lipoprotein (LDL) is a major carrier, containing micromolar concentrations of PlsEtns [20]. These chaperone proteins are critical since free plasmalogens are metabolically unstable. In the case of the blood-brain barrier and blood-retinal barrier, transport of the plasmalogens is via an LDL receptor-mediated transcytosis pathway that bypasses the lysosomal compartment [21].

This transport pathway preferentially shuttles LDL enriched in DHA-containing phospholipids [22]. LDL receptor function in AD and its potential impact on supply of plasmalogens to the CNS remain to be more clearly defined. In summary, there are a number of significant decrements in brain polyunsaturated fatty acids and PlsEtns in AD. These include early and dramatic decreases in white matter PlsEtns in the brain and a disease severity-dependent decrease in gray matter PlsEtns. These changes in lipid dynamics appear to be the result of peroxisomal dysfunction in both the liver [14] and brain [15,16], a conclusion further supported by the accumulation of VLCFAs in AD brain [15]. Since circulating plasmalogens are decreased in a number of other clinical conditions, the effects of these potential confounds need to be addressed in future AD studies.

These Brefeldin_A include plasmalogen decrements worldwide distributors in ischemic cerebrovascular disease [23], Parkinson’s disease [24], hypertension [25], uremia [26], and hyperlipidemia [27]. Choline glycerophospholipids Choline is an essential precursor for the synthesis of glycerophosphocholines (GPCs). However, choline levels are affected dramatically by agonal status and postmortem delays in human tissue handling. The net result is that there is no consistent finding from publications of choline levels in AD brain. However, as observed with PlsEtns, it appears there are decrements in brain choline plasmalogens (PlsChs; Figure ?Figure1)1) [28] but not in phosphatidylcholines [10]. These analyses were not performed with liquid chromatography-tandem mass spectrometry such that individual PlsChs were not characterized but fatty acid analyses did demonstrate deficits in the total DHA-containing PlsCh pool [28]. The PlsCh metabolite GPC has been shown to be increased in AD cortex [6] and CSF [29]. The accumulation of GPC is potentially indicative of increased degradation of choline glycerophospholipids and/or decreased GPC metabolism.