Plasmalogens and Alzheimer’s
Relation between Plasmalogens and Alzheimer’s
Plasmalogen is a subclass of phospholipids that is especially abundant in the brain, where it plays a vital role in structuring cell membranes and mediating signals. In Alzheimer’s disease (AD) patients, this key structural phospholipid decreases in the brain and serum. According to a study, decreased plasmalogen levels in the serum correlates to cognitive decline in AD patients. Hence, restoration of plasmalogen has the potential to improve the cognitive function of AD patients.
Reduced plasmalogen levels cause the following changes in Alzheimer’s disease brain:
- Further increment of ongoing oxidative damage.
- Alteration in membrane lipid composition and metabolism. Plasmalogens are essential for regulating membrane cholesterol dynamics. Plasmalogen deficiency increases membrane free cholesterol which subsequently facilitates the accumulation of amyloid β.
- Hypomyelination, which apparently determines the deterioration of cognitive function in Alzheimer’s disease.
- Neurodegeneration, synapse loss and synaptic (cholinergic system) dysfunction. This cholinergic dysfunction determines the cognitive decline in Alzheimer’s patients.
Several studies have shown that plasmalogens are reduced in the brain tissue and serum of Alzheimer’s patients. Serum plasmalogens decrease before the commencement of Alzheimer’s disease. The decline of circulating plasmalogens is associated with the severity of cognitive decline. In addition, scientists identified cognitive decline in subjects with plasmalogen levels less than 75% of the normal levels. Plasmalogen deficiency is hypothesised to negatively affect synaptic structure and function which possibly causes the synaptic dysfunction and neurotransmitter depletion as observed in Alzheimer’s disease.
Plasmalogen loss in the brain of Alzheimer’s disease is proposed to occur through several mechanisms:
- Peroxisome dysfunction. Decreased peroxisomal function leads to a reduced synthesis of plasmalogens.
- Oxidative damage. Reactive oxygen species (ROS) generated under oxidative stress in Alzheimer’s disease degrade plasmalogens in brain membrane. Increased oxidative damage has been shown in the brain with Alzheimer’s disease, which might due to factors such as age-related decline of energy availability, mitochondrial dysfunction and amyloid β (Aβ) accumulation.