Diet may explain the Nigerian Paradox, where they have among the highest rates of the Alzheimer’s susceptibility gene, ApoE4, but among the lowest rates of Alzheimer’s disease.
The Alzheimer’s Gene: Controlling ApoE
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Back in the 1990’s, a major susceptibility gene was discovered for Alzheimer’s, called ApoE4. If we have one ApoE4 gene, either from our mom or dad, like about 15% of the U.S. population do, our risk of getting Alzheimer’s is tripled, and if we’re like the 1 in 50 folks who have ApoE4 genes from both parents, we may be at nine times the risk.
The highest frequency of ApoE4 in the world is in Nigeria, but they also have some of the lowest Alzheimer’s rates. To understand this paradox, one has to understand the role of ApoE. What does the ApoE gene do? ApoE is the principal cholesterol carrier in the brain. So, the Nigerians’ diet appeared to have trumped their genes, due to their low cholesterol levels from their low intake of animal fat, living off of mainly grains and vegetables.
High ApoE4, but Alzheimer’s a rarity, thanks perhaps to low cholesterol levels, which any of us can achieve eating healthfully. These findings suggest that long-term changes in plasma cholesterol can lead to changes in ApoE gene expression. Just because we may have been dealt some bad genetic cards doesn’t mean we can’t reshuffle the deck with diet.
We cannot change our genetic makeup, but we can reduce or prevent high cholesterol. In this study of a thousand people for over 20 years, ApoE4 doubled the odds of Alzheimer’s, but high cholesterol nearly tripled the threat; so, the risk for Alzheimer’s disease from treatable factors—elevated cholesterol and blood pressure—appears to be greater than that from the dreaded Alzheimer’s susceptibility gene. In fact, projecting from their data, controlling lifestyle factors could reduce a person’s risk for Alzheimer’s disease, even if they have the double Apoe4 gene, from nine or ten times the odds down to just two.
People tend to have a fatalistic view toward developing Alzheimer’s disease, like it’s going to happen if it’s going to happen, but studies like this undermine such a view. We just need to emphasize the need for preventing and treating high blood pressure and cholesterol in the first place to reduce our risks for heart disease, stroke, and Alzheimer’s disease and, as a result, potentially enhance quantity and quality of life. Of equal importance, these data should be comforting to anyone interested in attempting to reduce the risk for and future burden of Alzheimer’s disease.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- B Sepehrnia, M Kamboh, L L Adams-Campbell, C H Bunker, M Nwankwo, P P Majumder, R E Ferrell. Genetic studies of human apolipoproteins. X. The effect of the apolipoprotein E polymorphism on quantitative levels of lipoproteins in Nigerian blacks. Am J Hum Genet. 1989 Oct;45(4):586-91.
- M Kivipelto, E L Helkala, M P Laakso, T Hänninen, M Hallikainen, K Alhainen, S Iivonen, A Mannermaa, J Tuomilehto, A Nissinen, H Soininen. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med. 2002 Aug 6;137(3):149-55.
- I L Notkola, R Sulkava, J Pekkanen, T Erkinjuntti, C Ehnholm, P Kivinen, J Tuomilehto, A Nissinen. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology. 1998;17(1):14-20.
- L Pugliell, R E Tanzi, D M Kovacs. Alzheimer's disease: the cholesterol connection. Nat Neurosci. 2003 Apr;6(4):345-51.
- S S Petanceska, S DeRosa, A Sharma, N Diaz, K Duff, S G Tint, L M Refolo, M Pappolla. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci. 2003;20(3):395-406.
- H C Hendrie, J Murrell, S Gao, F W Unverzagt, A Ogunniyi, K S Hall. nternational studies in dementia with particular emphasis on populations of African origin. Alzheimer Dis Assoc Disord. 2006 Jul-Sep;20(3 Suppl 2):S42-6.
- A D Roses, A M Saunders. APOE is a major susceptibility gene for Alzheimer's disease. Curr Opin Biotechnol. 1994 Dec;5(6):663-7.
- Evans RM, Emsley CL, Gao S, Sahota A, Hall KS, Farlow MR, Hendrie H. 2000. Serum cholesterol, APOE genotype, and the risk of Alzheimer's disease: a population-based study of African Americans. Neurology, 54(1):240-2.
- Hendrie HC, Murrell J, Gao S, Unverzagt FW, Ogunniyi A, Hall KS. International studies in dementia with particular emphasis on populations of African origin. Alzheimer Dis Assoc Disord. 2006;20(3 Suppl 2):S42-6.
Images thanks to PublicDomainPictures via Pixabay.
Back in the 1990’s, a major susceptibility gene was discovered for Alzheimer’s, called ApoE4. If we have one ApoE4 gene, either from our mom or dad, like about 15% of the U.S. population do, our risk of getting Alzheimer’s is tripled, and if we’re like the 1 in 50 folks who have ApoE4 genes from both parents, we may be at nine times the risk.
The highest frequency of ApoE4 in the world is in Nigeria, but they also have some of the lowest Alzheimer’s rates. To understand this paradox, one has to understand the role of ApoE. What does the ApoE gene do? ApoE is the principal cholesterol carrier in the brain. So, the Nigerians’ diet appeared to have trumped their genes, due to their low cholesterol levels from their low intake of animal fat, living off of mainly grains and vegetables.
High ApoE4, but Alzheimer’s a rarity, thanks perhaps to low cholesterol levels, which any of us can achieve eating healthfully. These findings suggest that long-term changes in plasma cholesterol can lead to changes in ApoE gene expression. Just because we may have been dealt some bad genetic cards doesn’t mean we can’t reshuffle the deck with diet.
We cannot change our genetic makeup, but we can reduce or prevent high cholesterol. In this study of a thousand people for over 20 years, ApoE4 doubled the odds of Alzheimer’s, but high cholesterol nearly tripled the threat; so, the risk for Alzheimer’s disease from treatable factors—elevated cholesterol and blood pressure—appears to be greater than that from the dreaded Alzheimer’s susceptibility gene. In fact, projecting from their data, controlling lifestyle factors could reduce a person’s risk for Alzheimer’s disease, even if they have the double Apoe4 gene, from nine or ten times the odds down to just two.
People tend to have a fatalistic view toward developing Alzheimer’s disease, like it’s going to happen if it’s going to happen, but studies like this undermine such a view. We just need to emphasize the need for preventing and treating high blood pressure and cholesterol in the first place to reduce our risks for heart disease, stroke, and Alzheimer’s disease and, as a result, potentially enhance quantity and quality of life. Of equal importance, these data should be comforting to anyone interested in attempting to reduce the risk for and future burden of Alzheimer’s disease.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- B Sepehrnia, M Kamboh, L L Adams-Campbell, C H Bunker, M Nwankwo, P P Majumder, R E Ferrell. Genetic studies of human apolipoproteins. X. The effect of the apolipoprotein E polymorphism on quantitative levels of lipoproteins in Nigerian blacks. Am J Hum Genet. 1989 Oct;45(4):586-91.
- M Kivipelto, E L Helkala, M P Laakso, T Hänninen, M Hallikainen, K Alhainen, S Iivonen, A Mannermaa, J Tuomilehto, A Nissinen, H Soininen. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med. 2002 Aug 6;137(3):149-55.
- I L Notkola, R Sulkava, J Pekkanen, T Erkinjuntti, C Ehnholm, P Kivinen, J Tuomilehto, A Nissinen. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology. 1998;17(1):14-20.
- L Pugliell, R E Tanzi, D M Kovacs. Alzheimer's disease: the cholesterol connection. Nat Neurosci. 2003 Apr;6(4):345-51.
- S S Petanceska, S DeRosa, A Sharma, N Diaz, K Duff, S G Tint, L M Refolo, M Pappolla. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci. 2003;20(3):395-406.
- H C Hendrie, J Murrell, S Gao, F W Unverzagt, A Ogunniyi, K S Hall. nternational studies in dementia with particular emphasis on populations of African origin. Alzheimer Dis Assoc Disord. 2006 Jul-Sep;20(3 Suppl 2):S42-6.
- A D Roses, A M Saunders. APOE is a major susceptibility gene for Alzheimer's disease. Curr Opin Biotechnol. 1994 Dec;5(6):663-7.
- Evans RM, Emsley CL, Gao S, Sahota A, Hall KS, Farlow MR, Hendrie H. 2000. Serum cholesterol, APOE genotype, and the risk of Alzheimer's disease: a population-based study of African Americans. Neurology, 54(1):240-2.
- Hendrie HC, Murrell J, Gao S, Unverzagt FW, Ogunniyi A, Hall KS. International studies in dementia with particular emphasis on populations of African origin. Alzheimer Dis Assoc Disord. 2006;20(3 Suppl 2):S42-6.
Images thanks to PublicDomainPictures via Pixabay.
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Title
The Alzheimer’s Gene: Controlling ApoE
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
What dietary changes? See some of my latest videos on preventing Alzheimer’s disease:
- Preventing Alzheimer’s with Lifestyle Changes
- Preventing Alzheimer’s Disease with Diet
- Preventing Alzheimer’s Disease With Plants
- Reducing Glycotoxin Intake to Prevent Alzheimers
- Alzheimer’s May Start Decades Before Diagnosis
- Alzheimer’s and Atherosclerosis of the Brain
- Cholesterol and Alzheimer’s Disease
-
Advanced Glycation End Products (AGEs) and Cognitive Decline
This concept of switching genes on and off is the exciting world of epigenetics. For more, see BRCA Breast Cancer Genes and Soy and Cancer Reversal Through Diet?
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