A recently published study investigated whether low-density lipoprotein (LDL) cholesterol may have a causal relationship with Alzheimer’s disease, Parkinson’s disease, and dementia.
Cholesterol serves as a component in the myelin sheath, a protective layer for neurons. Patients taking drugs that lower levels of cholesterol, such as statins, may be at risk of developing neurological conditions including Parkinson’s and Alzheimer’s disease. Statins target genes that code for the enzymes HMG-CoA reductase and PCSK9. These enzymes are responsible for the synthesis and metabolism of LDL cholesterol. Due to the close connections of LDL cholesterol and neurological function, it has been hypothesized that low LDL cholesterol levels may increase risk for neurological diseases. The British Medical Journal published a Mendelian randomization study to determine a potential causal relationship between low LDL levels and multiple neurological diseases.
Out of a total of 111 194 participants included in the study, 1001 were diagnosed with Alzheimer’s, 2154 suffered from dementia, 256 patients experienced vascular dementia, and 460 developed Parkinson’s disease. Researchers measured each participant’s LDL cholesterol levels. Plasma concentrations of the enzyme PCSK9 were measured using immunoassays with antibodies. High-density lipoprotein (HDL) cholesterol, and total cholesterol were also measured. Genotyping was carried out for genes pertaining to LDL cholesterol and statistical analyses were conducted on the resulting data. Outcomes included the risk of dementia and vascular dementia, Parkinson’s disease, and Alzheimer’s disease.
Results produced did not support the hypothesis. Genetic variation in the PCSK9 and HMGCR genes resulted in lower LDL cholesterol levels. The hazard ratio for relatively low LDL (< 1.8mmol/L) in comparison to higher LDL levels (> 4mmol/L) with respect to Parkinson’s disease was 1.7. There was no significant increase in risk factors between lower LDL and higher LDL cholesterol levels for Alzheimer’s disease, vascular dementia, and general dementia. In contrast to the generally insignificant results, there was an identifiable direct correlation between LDL cholesterol levels and the risk of Alzheimer’s disease. The data from this study suggests that there may be a connection between low LDL cholesterol levels and decreased risk of Alzheimer’s disease.
This novel research provides insight into the interconnected mechanisms of the human body. While the results may have disproved the hypothesis, they are valuable in terms of understanding the role of LDL cholesterol within the body. This information may encourage the development of drugs that target neurological conditions and cholesterol-related conditions exclusively, without increasing the risk of the other, or perhaps target both simultaneously. Medical professionals may also consider these results when recommending dietary intake with regards to a patient’s neurological state. Further exploration on the correlation between lower LDL levels and decreased risk of Alzheimer’s may be highly valuable for developing potential treatments.
Written By: Shrishti Ahuja, BSc