The Genetics of Alzheimer’s and Cardiovascular Diseases
Alzheimer’s Disease is a neural degenerative disease that causes worsening cognitive conditions. The symptoms include mental decline, confusion, delusions and memory loss. Due to these symptoms, patients present with several behavioral and psychological disabilities. Alzheimer’s can be a genetic disease and this disease has no cure. However, only a few drug and targeted therapies allows for the mitigation of the symptoms. On the contrary, Cardiovascular Disease is the number one cause of death as of 2019. Recent evidence indicates there may be a genetic connection between the two diseases. Furthermore, the potential drug treatments found by Dr. Catherine Kaczorowski from The Jackson Laboratory and Dr. Rahul Desikan from the University of California San Francisco, interconnect as they show how blood pressure medications, formally known as, Metformin hydrochloride, could potentially be used to treat both Cardiovascular Disease and Alzheimer’s. Although both proposed different research methods, their research overall created a distinct connection to both the use of genetics for Cardiovascular and Alzheimer’s Disease.
Dr. Desikan and his colleagues used genome-wide association studies (GWAS) – a type of genetic study which allows statistical links between several diseases and their shared variations within the genetic code. Desikan’s team analyzed patients presenting with Alzheimer’s disease and individuals with Cardiovascular disease. They combined these genetic markers and identified 90 spots in the genome “where specific DNA variants increased patients’ combined chance of developing both Alzheimer’s disease and heightened blood levels of lipid molecules” (). These lipid molecules include HDL and LDL cholesterol and triglycerides. Furthermore, six of the 90 regions had very significant effects in both diseases located on chromosome 11. These results suggested Alzheimer’s and Cardiovascular diseases could potentially be linked to each other. This is essential for drug therapies to design possible delay or prevent the onset of Alzheimer’s disease. Dr. Desikan’s team confirmed their findings with collaboration with Celeste M. Karch, an Alzheimer’s expert at Washington University School of Medicine in St. Louis. Karch’s team indicates novel genes closely associated with Alzheimer’s and Cardiovascular risks. However, these genes were differently expressed in the brains of Alzheimer’s patients compared to the brains of the control group. Ultimately, Dr. Desikan’s findings of genetic modulation between the connection of Cardiovascular Disease and Alzheimer’s Disease can create potential drug therapies. Additionally, the discovery of the markers on specific genes allows for drug targets to be generated.
Similarly, Dr. Kaczorowski demonstrates the usage of Hp1bp3 gene as a key modulator of cognitive aging. She detects that a reduced expression of Hp1bp3 is observed in both cognitively impaired aged mice and humans. This indicates that a decreased expression contributes to cognitive aging and dementias such as Alzheimer’s disease. Hp1bp3 is amongst the top 100 genes that are upregulated in response to metformin hydrochloride. This drug was used to enhance memory in mice and recently approved for clinical trials to reduce the effects of cognitive decline. Metformin Hydrochloride is also used as a blood pressure medication to prevent Cardiovascular Diseases in humans. Overall, the research done by Dr. Kaczorowski suggests the usage of Hp1bp3 could possibly serve as potential targets against cognitive aging. HP1BP3 protein levels are significantly reduced in the hippocampi of individuals with cognitive disabilities, especially elder humans. Furthermore, deletion of the function Hp1bp3 causes memory deficits in mice and humans which further supports the claim of Hp1bp3 as a modulator in cognitive decline and aging.
Alzheimer’s and Cardiovascular Diseases are both highly prevalent. The research of Dr. Desikan indicates that both diseases are linked, and Alzheimer’s is seen to have cardiovascular side-effects. Unfortunately, Alzheimer’s does not have a cure, but based on the research of Dr. Kaczorowski and Dr. Desikan, potential drug therapies can be created due to the specific genetic locations identified. The hope for precision medicine to prevent or delay the onset of Alzheimer’s disease is seen throughout both studies. Furthermore, Dr. Desikan continues to integrate his findings into his lab’s developed polygenic risk score, which allows clinicians to calculate a patient’s risk for the development of both Cardiovascular and Alzheimer’s Disease. Dr. Kaczorowski also indicates that drug therapies can target diseases of cognitive aging and not just Alzheimer’s Disease. These diseases would include Tau mutations, Parkinson’s, and Dementia. Additionally, the linkage of Cardiovascular Disease to Alzheimer’s Disease provides assurance as the knowledge for Cardiovascular Disease is greatly known and can aid in preventing or offsetting Alzheimer’s Disease. Both Dr. Desikan and Dr. Kaczorowski are on the right path to help find potential drug therapies against Alzheimer’s Disease.
References
Iris J. Broce, Chin Hong Tan, Chun Chieh Fan, Iris Jansen, Jeanne E. Savage, Aree Witoelar, Natalie Wen, Christopher P. Hess, William P. Dillon, Christine M. Glastonbury, Maria Glymour, Jennifer S. Yokoyama, Fanny M. Elahi, Gil D. Rabinovici, Bruce L. Miller, Elizabeth C. Mormino, Reisa A. Sperling, David A. Bennett, Linda K. McEvoy, James B. Brewer, Howard H. Feldman, Bradley T. Hyman, Margaret Pericak-Vance, Jonathan L. Haines, Lindsay A. Farrer, Richard Mayeux, Gerard D. Schellenberg, Kristine Yaffe, Leo P. Sugrue, Anders M. Dale, Danielle Posthuma, Ole A. Andreassen, Celeste M. Karch, Rahul S. Desikan. Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease. Acta Neuropathologica, 2018; DOI: 10.1007/s00401-018-1928-6
University of California – San Francisco. (2018, November 9). Alzheimer’s and cardiovascular disease share common genetics in some patients. ScienceDaily. Retrieved February 27, 2021 from www.sciencedaily.com/releases/2018/11/181109155521.htm
Neuner, Sarah M., et al. “Systems Genetics Identifies Hp1bp3 as a Novel Modulator of Cognitive Aging.” Neurobiology of Aging, vol. 46, 2016, pp. 58–67., doi:10.1016/j.neurobiolaging.2016.06.008.
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