Article Originally published on Linkedin August 3rd, 2018.
Neurodegenerative diseases are easily described as the progressive loss of the cells that make up our nervous system (neurons and glial cells). There are numerous degenerative disorders and they vary according to their clinical symptoms and pathology. One of the well-known neurodegenerative diseases is Alzheimer’s disease (AD). Dr. Alois Alzheimer first described it as presenile dementia in the early 1900s caused by abnormal plaques and tangles in the brain (more to come on these).
AD is of interest to researchers today for many reasons. First, it is a disease that isn’t restricted to an individuals’ age, sex, race or creed. Although, AD has been classified as an aging disorder, it is becoming clearer that the presence of the disease indicates that older brains may be more susceptible to the disease [1]. Secondly, the disease poses a great challenge to researchers and clinicians as we try to develop treatment options and find mechanisms to diagnose and stop its progression. Thirdly, the worldwide impact of AD in the coming years is of great concern as the expected financial burden on patients, their family members, caregivers and society as a whole is expected to increase tremendously.
Over the years, a lot of progress has been made in trying to increase our understanding of the disease. In 1993, the first genetic risk factor for Alzheimer’s disease was identified [2]. This gene known as apolipoprotein E (APOE) is the major cholesterol carrier in the brain that supports lipid transport and the repair of damage in brain cells [3]. The gene has several variations but APOEe4 is the variant that increases our risk for AD. There have also been other genes like presenilin 1 (PSEN1) and presenilin 2 (PSEN2) that have been identified and one current goal of researchers is to identify more risk associated genes.
One striking thing about APOEe4 is the fact that in 1989, before the gene was linked with Alzheimer’s disease, some studies showed Nigerians had the highest frequency ofAPOEe4 variant in the world [4, 5]. Yet, they also seemed to have the lowest observed rate of AD [6]. Similar results were observed in East Africans from Kenya and Tanzania [7, 8]. However, when the same study was conducted with African Americans in the U.S., the results showed the complete opposite [9]. There was a link between individuals that carried the APOE e4 variant and the development of Alzheimer’s disease in the U.S with the main difference being their blood cholesterol levels. Knowing this, a clinical trial was carried out to see if lowering blood cholesterol levels affected an individual’s AD progression from mild to severe and they found that lowering cholesterol levels did not make a difference [10].
The concept of epigenetics tells us that there is a link between our environment, and how diseases manifest in us as individuals. Meaning that although we cannot change our genetic make up, environmental factors can still modify how our genes function and these studies seem to prove that. With that being said, it is also important to understand that genes don’t function singularly but as networks. Understanding the signals within these networks may give us a better insight into diagnosing and preventing AD.
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10. Sano, M., et al., A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease.Neurology, 2011. 77(6): p. 556-63.
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