Alzheimer's Linked to Cholesterol Gene

People with a specific gene type may be able to cut their risk of developing Alzheimer’s disease by altering their cholesterol profile, a recent study suggests. About a fifth of the population carries a single copy of the ApoE4 allele, a version of the ApoE gene, and have a raised risk of Alzheimer’s disease. A further two percent carries two copies (one from each parent) of this gene variant, and their risk of Alzheimer’s is extremely high.

A team of researchers from Heidelberg University, Germany, examined figures from two separate studies of ApoE4 carriers. They explain that ApoE stands for apolipoprotein E, a protein that plays a vital role in blood lipid metabolism. This protein transports the necessary cholesterol to nerve cells.

Dr. Laura Perna and her team used blood samples and medical information from two studies of older adults. This was compared against results of memory and concentration tests. The studies included 1,800 participants over 50 years of age.

Results indicated that the ApoE4 allele was most closely linked to cognitive deficits, especially memory, among those with high cholesterol and heart disease. Such cognitive deficits can be harbingers of dementia and Alzheimer’s, but they can also arise independently.

Dr. Perna says, “One possible explanation for the results could be that the brain is especially sensitive to the effects of ApoE4 once it has already been affected by cardiovascular disease and high cholesterol. It is most likely a complex interaction between the various factors.

“The ApoE4 allele not only increases the risk of Alzheimer’s, but is also associated with an increased risk of arteriosclerosis [hardening of the artery walls]. Arteriosclerosis also supports the development of dementia.”

Professor Hermann Brenner of the German Cancer Research Center also worked on the study. He points out, “Both high cholesterol and cardiovascular disease are potentially avoidable, and in many cases a healthy diet and lifestyle can reduce high cholesterol. Regular exercise and a diet rich in vegetables and fruit help keep cholesterol levels down. What’s good for the heart is also good for the brain and memory. This appears to be especially important for carriers of the ApoE4 risk factor.”

Findings appear in the journal Dementia and Geriatric Cognitive Disorders. The researchers say about ApoE4, “The possible prevention of its detrimental effects on cognition is of high relevance.” Their results indicate “The association of ApoE4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease.”

They add, “Hypercholesterolemia was associated with cognitive function only among ApoE4 carriers in the presence of cardiovascular disease,” concluding, “The detrimental effects of ApoE4 polymorphism on cognition may strongly depend on modifiable risk factors.”

Could a higher intake of omega-3 fatty acids work to protect cognitive function among ApoE4 carriers? In the general population, consuming omega 3 fatty acids (oily fish is a good source) seems to be associated with a lower risk of developing both Alzheimer’s disease and coronary heart disease. However, this link appears not to hold in ApoE4 carriers.

The omega-3 fatty acid called docosahexaenoic acid is an essential molecule for healthy neurons. Docosahexaenoic acid consumption is thought to be protective against late onset Alzheimer’s disease via at least 12 neuroprotective effects. These include effects on the central nervous system that may protect against ApoE4-related cognitive decline.

But ApoE4 carriers do not appear to be protected against cognitive decline by a high oily fish-containing diet. In one recent study of patients with late-onset Alzheimer’s disease, only those not carrying ApoE4 had a decreased rate of cognitive change when taking docosahexaenoic acid, as compared with placebo.

The researchers in this study, from Oregon Health and Science University, Portland, OR, state, “Several epidemiological studies indicate that a protective effect of omega-3 fatty acids with respect to dementia may be confined to ApoE4-negative individuals.”

Conversely, a study from Wageningen University in The Netherlands found that higher levels of docosahexaenoic acid in plasma was linked to a slower decline in memory among ApoE4 carriers. Furthermore, an increased consumption of docosahexaenoic acid via supplement was shown to improve attention scores in healthy elderly individuals carrying ApoE4, compared with placebo. Hence, ApoE4 carriers may benefit from an omega-3 supplement.

Clearly, further trials are needed to confirm a benefit from omega-3 fatty acids, in light of these mixed results. But the evidence all seems to point to a different fatty acid metabolism among those individuals with the e4 version for the APOE gene, and that this difference may hold the key to an effective method of reducing dementia risk.


Perna, L. et al. Apolipoprotein E e4 and cognitive function: a modifiable association? Results from two independent cohort studies. Dementia and Geriatric Cognitive Disorders, 24 October 2015 doi: 10.1159/000440697

Quinn, J. F. et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial. The Journal of the American Medical Association, 3 November 2010 doi: 10.1001/jama.2010.1510

van de Rest, O. et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology, 5 August 2008.