First some background. Contrary to popular belief, most cells in the brain are not neurons, but are glial cells that support, protect and nourish the neurons and outnumber them 5 to 1. Astrocytes are specialized 'star-shaped' glial cells that produce a lipid transport protein called apoprotein E (ApoE) whose job it is to transport lipids and cholesterol to neurons. The human gene that encodes for ApoE has three well known SNPs (single nucleotide polymorphisms, or misspellings) resulting in three variants ApoE2, ApoE3 and ApoE4. People with the ApoE4 variant do not transport fats effectively leading to accumulation of lipid (adipose saccules) in glial cells - an observation which is associated with many neurodegenerative diseases, including Alzheimer's disease.

If one parent has the ApoE4 variant and the other parent doesn't, then the offspring is described as having one ApoE4 allele. This is prevalent in approximately 25% of the global population. However, it has been found that 65-80% of people who develop Alzheimer's disease have at least one ApoE4 allele. In other words, having this form of ApoE increases the risk of developing Alzheimer's 2-3 fold. If a person inherits ApoE4 from both parents (ie has both ApoE4 alleles) this increases the risk for Alzheimer's as much as 15-fold.

No wonder the MIT scientists from the Department of Brain and Cognitive Sciences wanted to explore the cause of the ApoE4 disruption and created an ApoE model in a baker's yeast cell line to reproduce exactly what was going on in the human astrocyte cell. The growth rate for ApoE4 yeast cells was significantly less than the ApoE3 yeast cells, except when provided with an enriched medium - suggesting that availability of the right 'nutrient' could reverse the ApoE4 defect. Another experiment suggested that the growth defect could be related to the production of phospholipids for cell membranes (see X Fact Why Phospholipids Are So Important...).

This inspired the researchers to add two precursors of phospholipid synthesis to the culture medium - ethanolamine and choline. Ethanolamine didn't do the trick, but choline did and essentially nullified the growth retarding effect of ApoE4 on these yeast cells. Furthermore, choline also reduced the lipid droplet accumulation within the ApoE4 expressing yeast cell. The findings were then cross-checked back in the human astrocyte model and the exact same effects were observed. Choline, metabolized via the Kennedy Pathway to produce phosphatidylcholine is able to reverse the negative affects of the ApoE4 variant on the human brain and could play a significant role in prevention and mitigation of Alzheimer's disease.

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