Researchers Discover Clues to Link Between Cholesterol and Alzheimer's Disease

The finding that cholesterol can cause chromosomal aberrations common to Alzheimer’s disease and Down syndrome may help lead to new therapies.

Researchers have known for some time that cholesterol damages the brain, thereby increasing the risk of Alzheimer’s disease, but they have never understood quite how. Now, researchers at the Linda Crnic Institute for Down Syndrome and the University of Colorado School of Medicine may have solved the puzzle.

Through studies of Niemann-Pick type C disease and Down syndrome, the researchers observed how cholesterol (especially LDL, or “bad,” cholesterol) disturbs cell division such that aberrant daughter cells result. Their study was published in the online journal PLOS ONE on April 12, 2013.

Cholesterol causes malfunctions during cell division in mice and humans such that replicated chromosomes are incorrectly distributed to daughter cells. As a result, daughter cells will often receive 1 or 3 copies of each chromosome instead of the normal pair. Researchers have found that cholesterol can cause daughter cells to receive 3 copies of chromosome 21, which is responsible for the code for amyloid peptide. Amyloid peptide is the main ingredient in the neurotoxic amyloid filament found in Alzheimer’s patients’ brains.

Down syndrome patients also have cells with 3 copies of chromosome 21 (known as trisomy 21 cells), although they have the cells from conception. Moreover, Alzheimer’s patients develop the same brain pathology as do those with Down syndrome. Based on these parallels between the conditions, the researchers suggest that Alzheimer’s can be seen as a form of acquired Down syndrome.

The researchers also found trisomy 21 neurons in children with Niemann-Pick type C, a neurodegenerative disease. Until now, researchers had found no connection between Down syndrome and Niemann-Pick type C disease.

The researchers suggest that their discoveries have the potential to open many new avenues for research and therapy. Other researchers have already demonstrated a simple in vitro approach that prevents cholesterol from causing unequal chromosome distribution. These researchers found that LDL exposure did not affect cell division in cultures treated with ethanol. More study is needed to determine if or how their findings will apply to treatment of people.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.