How ApoE4 Increases Risk of Alzheimer’s Disease

canstockphoto1099462Since genetic testing has come into vogue, the ApoE4 protein has become famous or – should we say – infamous. Many people know that if they carry the gene, it increases their risk of developing Alzheimer’s disease by a factor of 10. ApoE4 affects the clearance of amyloid- beta, the plaque that builds up in the brains of Alzheimer’s disease patients. So it would be great to know more about how ApoE4 causes such problems.

Research from the lab of Dr. Dale Bredesen may provide answers to that. Living the CR Way members will remember Dr. Bredesen and his outstanding teleconference on Alzheimer’s.

Last year, Dr. Bredesen and colleagues from his lab discovered that ApoE4 causes a dramatic reduction of SIRT1, one of the CR Way’s favorite genes, which is associated with longevity and reduced risk of many age-related diseases. Bredesen and his colleagues discovered that decreased SIRT1 affects amyloid precursor protein (APP), which is critical for the brain’s management of memory.

Apparently, when SIRT1 decreases, APP goes in the direction of memory loss. Dr. Bredesen’s lab is looking for drugs that will maintain levels of SIRT1. However, LivingTheCRWay members don’t have to wait because you follow a lifestyle that increases SIRT1 activity naturally. The CR Way to Great Glucose Control with its emphasis on reduced calories, lower glucose, moderate protein are all critical to robust activation of the SIRT1 gene. So is circadian living, as the SIRT1 gene controls other genes activated by light and dark cycles.

Recently, we’ve included new tests in the CR Way DNA HACR testing protocol that involve the eyes. Given that the eyes reflect what’s going on in the brain, you will not be surprised to learn that SIRT1 is also involved in ocular aging.

The role of SIRT1 in ocular aging.

Experimental eye research. 2013 Nov;116:17-26. doi: 10.1016/j.exer.2013.07.017. Epub 2013 Jul 26.

Mimura T, Kaji Y, Noma H, Funatsu H, Okamoto S


…The available data indicate that SIRT1 is localized in the nucleus and cytoplasm of cells forming all normal ocular structures, including the cornea, lens, iris, ciliary body, and retina. Upregulation of SIRT1 has been shown to have an important protective effect against various ocular diseases, such as cataract, retinal degeneration, optic neuritis, and uveitis in animal models. These results suggest that SIRT1 may provide protection against diseases related to oxidative stress-induced ocular damage, including cataract, age-related macular degeneration, and optic nerve degeneration in glaucoma patients.

PMID: 23892278. U.S.NIH, U.S.NLM, PubMed access to Medline

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