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Untangling the link between high cholesterol and Alzheimer's

Many studies have revealed a link between high cholesterol levels and Alzheimer’s disease (AD), but the question of cause and effect remains unclear: does higher cholesterol lead to Alzheimer’s, or could it be the other way around?

New research from King’s College London, published in PLOS Medicine, suggests that cholesterol does not directly increase the risk for late-onset Alzheimer’s disease. The researchers looked at genetically raised cholesterol levels, but add that the study cannot draw conclusions about diet, lifestyle and medications which may also be associated with increased risk of AD, independently of their effects on cholesterol levels.

Approximately 44 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, communication, and other cognitive functions. Alzheimer’s disease is the most common form of dementia, and is caused by the formation of protein deposits in the brain that lead to the loss of brain cells.  Previous studies have found an association between increased cholesterol in the blood of people in midlife and the risk of Alzheimer’s disease later in life.

The authors used DNA genotype data from 10,578 participants, including 3,914 individuals with AD, 1,675 older individuals without AD and 4,989 participants from the general population. For each participant the authors calculated a genotype risk score (GRS) – that is, whether they are genetically more likely to have increased cholesterol, triglycerides and what is called “good” and “bad” cholesterol. They found there was no association between the participant’s lipid GRS and AD.

Dr Petroula Proitsi, Alzheimer’s Society Research Fellow at the Department of Basic and Clinical Neuroscience at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s, and lead author of the study says: “Many studies show that cholesterol is important in Alzheimer’s disease. However, what we don’t know is how it is associated with Alzheimer’s and whether elevated cholesterol in the blood leads to Alzheimer’s disease later in life or whether it is an early consequence of undiagnosed Alzheimer’s disease.  We find that genetically raised cholesterol levels confer no increased risk for Alzheimer’s disease.”

Professor John Powell, senior author of the study from the IoPPN at King’s, says: “By looking at genes which do not change over time, we can study the link between cholesterol and Alzheimer’s disease without the influence of other environmental factors, such as diet, lifestyle, age etc. We know there is an association between cholesterol and Alzheimer’s disease, but our findings suggest this is not a direct cause and effect, but likely to be something more complex.”

Dr Proitsi adds: “These findings have implications for both future research into the causes of Alzheimer’s disease, and treatment strategies.  Cholesterol levels are a potentially modifiable risk factor, which could be targeted through pharmacological or lifestyle interventions. If elevated cholesterol in the blood does not lead to AD, then interventions, such as statins for example that reduce cholesterol levels would not necessarily reduce the risk for AD.  However, there is a wide range of evidence showing that high levels of cholesterol are bad for our health, and that a healthy, balanced diet is likely to be good for both our physical as well as mental health.”

The research was primarily funded by the EMBO and the UK Alzheimer’s Society.

Paper reference: Proitsi, P. et al. 'Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis' published in PLOS Medicine DOI: 10.1371/journal.pmed.1001713