Alzheimer’s disease remains a puzzle.
Although there are plenty of people who claim that “The Cause” of Alzheimer’s is… and here you can take your pick of three-dozen theories.
The truth of the matter is that simple explanations - Aluminum, lead, stress, pollution, mycoplasma infections and the rest – fail to explain many of the established observations about the causes of the disease.
From what we know about the genes in the brain, it is highly likely that “Alzheimer’s disease” represents a group of disorders that follow an interaction of sets of genetic and environmental factors.
This notion is supported by a report from investigators at Washington University School of Medicine, St. Louis and several other prominent research centers. The study is published in today’s issue of the journal Neuron and indicates that there a biological link between a protein mutation that causes early-onset Alzheimer's disease (AD) and a gene variant linked to late-onset AD.
The investigators tried to link the function of two known causative factors in AD. Mutations in amyloid precursor protein (APP) cause early-onset Alzheimer's disease (AD), but the only genetic risk factor for late-onset AD is the ɛ4 allele of apolipoprotein E (apoE), a major carrier of cholesterol in the circulation and in cell membranes.
Previous research has shown that mutations in APP can cause early-onset AD when the protein is “cleaved” or split, producing a short toxic protein that builds up in the brain and kills neurons.
In their experiments with mice and cultured mouse cells, the researchers linked APP to the regulation of apoE and its cholesterol transport function. They found that the normal cleavage of APP in the cell gives rise to a nontoxic fragment (called AICD) that suppresses the gene that produces the cell receptor for apoE, known as LRP1. Crouching in nerve cell membranes, this receptor enables the apoE protein to transport its cholesterol cargo into the cell.
The researchers speculated that the loss of LRP1 function in AD might cause a loss of cholesterol that causes malfunction of neurons.
These observations may turn out to be extremely important. If we can restore the activity of the receptor gene, we might have a new treatment strategy for AD.