Alkyl-Acylglycerols and the Important Clinical Ramifications of Raising Plasmalogens in Dementia and Alzheimer's Disease.

A critical factor involved in the pathophysiology of Alzheimer's disease (AD) and related dementias is the decline of plasmalogens, a key glycerophospholipid required for normal neuron function. An accumulating body of evidence correlates low blood and brain plasmalogens with higher levels of AD pathology and lower cognition scores and indicates that declines in these phospholipids begin years before clinical symptoms develop. Furthermore, it has been recently reported that high blood plasmalogen levels neutralize the increased risk of dementia in persons who carry the APOE epsilon 4 allele, the most significant genetic risk factor for AD. There are over 30 common species of plasmalogens in the human body with different plasmalogen species playing different roles, depending on the organ and cell type. Accordingly, there is great interest in understanding how to selectively target plasmalogen augmentation for specific health needs. For example, brain white matter is comprised of plasmalogens containing monounsaturated fatty acids, whereas gray matter is comprised of plasmalogens containing polyunsaturated fatty acids. Fortunately, the structure-activity and biochemistry of plasmalogen augmentation has been extensively studied in cell and animal models. Restoring and augmenting levels of selective plasmalogens can be achieved with dietary supplementation of 1-O-alkyl-2-acyl glycerol oils containing the desired fatty acid type at the 2-acyl position. Neuron-targeted 1-O-alkyl-2-acyl glycerol containing DHA has been shown to be neuroprotective and neuroactive in animal models of neurodegeneration. This review will discuss the mechanisms by which plasmalogen deficiency leads to Alzheimer's and/or dementia and the critical role that 1-O-alkyl-2-acyl glycerol oils can play in patients with those disorders.