Inspecting The Influences on Alzheimer’s Disease Development

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that leads to gradual loss of function in motor skills and cognitive function of patients. As the most common type of dementia, Alzheimer’s impacts over 5 million Americans who are 65 and older, and this number is projected to rise to almost 14 million by 2050 (1). Furthermore, this shocking statistic makes evident  the need to seek out treatment and preventative measures in the coming years. AD is known to have some genetic inheritance, leading AD patient families to wonder – How can I know if I’m at risk? What indicates my likelihood of developing Alzheimer’s in the future? Though genetics do influence one’s probability of an AD diagnosis, genetics are not the only risk factor for AD development.

Environmental and genetic factors alike can influence the eventual prognosis of Alzheimer’s disease. Smoking, failure to maintain a healthy routine, and other outstanding circumstances, such as exposure to toxic substances via air pollution, can play a role in long term environmental development of AD (2). Geographical variation may also factor into disease progression, as it’s been shown living in rural areas during early life leads to higher percentages of AD in populations when compared to overall incidences in larger, more developed regions (3). AD and dementia alike are affected by risk and protective factors throughout the course of life such as continued learning and dietary choices (4). 

Unlike environmental factors, genetic factors impacting AD are inherited and cannot be prevented in the same manner as certain environmental influences. Individuals in a family in which one or more persons have received an AD prognosis or other forms of dementia are at increased risk for being diagnosed with AD later in life. Age at onset (AAO) of AD is a metric by which researchers gauge treatment or prevention efficacy for finding suitable Alzheimer’s therapies. AAO may be predicted by looking at familial genomes for genetic markers. Variants at these critical genome segments may provide insight for showing if (or when) an individual will develop AD (5).

Certain instances of Alzheimer’s development have been earmarked by rare mutations in the APP, PSEN1, and PSEN2 genes that are specifically characterized by early-onset AAO. Common causes of AD have been identified by looking at multiple individuals within larger populations. Gene variants in APOE, TREM1, and PLD3 are most common in these studies, suggesting their larger key roles in causing disease  (5, 7). Studies focusing on familial pedigrees where a handful of individuals are studied present key, rare traits that highlight AD development and provide researchers with genetic loci to pursue for possible therapeutic interventions. Population-wide studies lend themselves to identifying key genes of interest that commonly lead to AD development. 

Overall, identifying the genetic cause of AD is difficult due to the wide variety of potential causes. Individual mutations at key loci in the genome or damage to the brain of any capacity can trigger eventual AD onset. It is difficult to target key genes that would be suited for therapeutic creation when population-wide variation suggests different causes between individuals (6). Targeting pathways and mechanisms that lead to Alzehimer’s disease development is a maze of genes and can be interrupted or impacted by a variety of activities, choices, and circumstances that make up day-to-day life (7). 

1. Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013). Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology, 80(19), 1778–1783. https://doi.org/10.1212/WNL.0b013e31828726f5
2. Killin, L. O., Starr, J. M., Shiue, I. J., & Russ, T. C. (2016). Environmental risk factors for dementia: a systematic review. BMC geriatrics, 16(1), 175. https://doi.org/10.1186/s12877-016-0342-y
3. Russ, T. C., Batty, G. D., Hearnshaw, G. F., Fenton, C., & Starr, J. M. (2012). Geographical variation in dementia: systematic review with meta-analysis. International journal of epidemiology, 41(4), 1012–1032. https://doi.org/10.1093/ije/dys103
4. Whalley, L. J., Dick, F. D., & McNeill, G. (2006). A life-course approach to the aetiology of late-onset dementias. The Lancet. Neurology, 5(1), 87–96. https://doi.org/10.1016/S1474-4422(05)70286-6
5. Saad, M., Brkanac, Z., & Wijsman, E. M. (2015). Family-based genome scan for age at onset of late-onset Alzheimer’s disease in whole exome sequencing data. Genes, brain, and behavior, 14(8), 607–617. https://doi.org/10.1111/gbb.12250
6. Reitz C. (2015). Genetic diagnosis and prognosis of Alzheimer’s disease: challenges and opportunities. Expert review of molecular diagnostics, 15(3), 339–348. https://doi.org/10.1586/14737159.2015.1002469
7. Karch, C. M., Cruchaga, C., & Goate, A. M. (2014). Alzheimer’s disease genetics: from the bench to the clinic. Neuron, 83(1), 11–26. https://doi.org/10.1016/j.neuron.2014.05.041