“Autocannibalism” of choline-containing membrane phospholipids in the pathogenesis of Alzheimer's disease—A hypothesis

The selective vulnerability of certain cholinergic neurons in Alzheimer's disease could reflect a unique response of these neurons to a neurotoxic factor. Alternatively the etiologic factor causing the disease could affect the brain generally, and the selective death of the cholinergic neurons could occur because they have a biochemical property that makes them least able to withstand this factor. One such property might be their tendency to utilize choline-phospholipids both as a membrane constituent and as a source of free choline for acetylcholine synthesis: perhaps when choline levels in the brain's extracellular fluid are too low to sustain acetylcholine release, these neurons break down their choline-phospholipids more rapidly than they can synthesize them, thus changing membrane structure and, ultimately, neuronal viability.