The Link Between Alzheimer’s Disease and Traumatic Brain Injuries
DOI:
https://doi.org/10.58445/rars.1127Keywords:
Alzheimer's Disease, Traumatic Brain Injury, current treatmentsAbstract
Alzheimer's Disease (AD), a neurological disorder that impairs a person’s cognitive abilities, is expected to impact 13.8 million Americans by 2060. Causes of AD are unknown, however, factors that can lead to AD include a combination of aging, genetic propensities, environmental and lifestyle factors. Additionally, studies have shown that adults with a history of a moderate traumatic brain injury (TBI) had a 2.3 times greater risk of developing AD and those with a history of a severe TBI had a 4.5 times greater risk. The enhanced risk is driven by the empirical evidence that changes in neural tissue due to TBIs exhibit similar aberrations to AD. Both TBIs and AD share similar pathological abnormalities such as accumulation of amyloid plaques and tau proteins, cell membrane damage, and organelle dysfunction. The purpose of this review is to 1) explore the cerebral and physiological link between TBIs and AD, 2) discuss studies that examine this link by isolating different factors that lead to the accumulation of Aβ/tau deposition leading to AD-like pathology, and 3) discuss current treatments currently used to slow the progression of Alzheimer's. While research has established an association between TBIs and an increased risk of developing AD, a conclusive link has yet to be established. The challenge is distinguishing between the neurodegenerative impact of a TBI and the natural pathological changes due to genetic factors and other risk factors of AD. Additional research is necessary to build upon evidence from past studies to determine a causal link between TBIs and AD.
References
Montana DPHHS. (2020). Neurological Disorders. Mt.gov. https://dphhs.mt.gov/schoolhealth/chronichealth/neurologicaldisorders#:~:text=Neurologic al%20disorders%20are%20medically%20defined
Van Schependom, J., & D’haeseleer, M. (2023). Advances in Neurodegenerative Diseases. Journal of Clinical Medicine, 12(5), 1709. https://doi.org/10.3390/jcm12051709
Number of People Living With Brain Disease Expected to Double by 2050. (n.d.). Wfneurology.org.
https://wfneurology.org/activities/news-events/archived-news/2023-10-16-wcn Neurodegenerative Diseases. (n.d.). National Institute of Environmental Health Sciences.
Retrieved March 30, 2024, from https://www.google.com/url?q=https://www.niehs.nih.gov/research/supported/health/neur odegenerative&sa=D&source=docs&ust=1711840582276368&usg=AOvVaw1Oz90vSSc nlt-N0_p9q51d
Alzheimer’s Disease Facts and Figures. (n.d.). Alzheimer’s Association. Retrieved March 30, 2024, from https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf
Alzheimer's Association. (2023). 2023 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 19(4), 1598–1695. https://doi.org/10.1002/alz.13016
CDC. (2021, April 7). What is Alzheimer’s Disease? | CDC. Www.cdc.gov. https://www.cdc.gov/aging/aginginfo/alzheimers.htm#:~:text=Alzheimer%27s%20disease %20is%20the%20most
National Institute of Neurological Disorders and Stroke. (2022, September 27). Brain Basics: The Life and Death of a Neuron | National Institute of Neurological Disorders and Stroke. Www.ninds.nih.gov. https://www.ninds.nih.gov/health-information/public-education/brain-basics/brain-basics-lif e-and-death-neuron#:~:text=Neurons%20are%20information%20messengers.
National Institute on Aging. (2023, April 5). Alzheimer’s Disease fact sheet. National Institute on Aging.
https://www.nia.nih.gov/health/alzheimers-and-dementia/alzheimers-disease-fact-sheet Alzheimer’s: Brain changes may occur 34 years before symptoms. (2019, May 21).
Www.medicalnewstoday.com. https://www.medicalnewstoday.com/articles/325235 National Institute on Aging. (2019, December 24). What causes Alzheimer’s disease? National
Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-causes-alzheime rs-disease
Alzheimer's Association. (2016). Traumatic Brain Injury (TBI). Alzheimer’s Disease and Dementia.
https://www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions/traumatic-b
rain-injury#:~:text=The%20key%20studies%20showing%20an
What Happens to the Brain in Alzheimer’s Disease? (2024, January 19). National Institute on
Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-al zheimers-disease#:~:text=The%20healthy%20human%20brain%20contains,and%20org ans%20of%20the%20body.
How do neurons work? (2017, November 9). Uq.edu.au. https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/how-do-neurons-work
Moyes and Schulte. (n.d.). Neurons: Passive potentials. Retrieved March 30, 2024, from https://www.zoology.ubc.ca/~gardner/neurons-passive%20potentials.htm
Kumar, A., Tsao, J. W., Sidhu, J., & Goyal, A. (2022, June 5). Alzheimer Disease. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK499922/
Amyloid plaques. (2021, February 19). Wikipedia. https://en.wikipedia.org/wiki/Amyloid_plaques Takasugi, N., Masato Komai, Kaneshiro, N., Ikeda, A., Yuji Kamikubo, & Uehara, T. (2023). The
Pursuit of the “Inside” of the Amyloid Hypothesis—Is C99 a Promising Therapeutic Target
for Alzheimer’s Disease? 12(3), 454–454. https://doi.org/10.3390/cells12030454 Figure 6 Major pathological hallmarks of AD are amyloid plaques and... (n.d.). ResearchGate.
https://www.researchgate.net/figure/Major-pathological-hallmarks-of-AD-are-amyloid-plaq
ues-and-neurofibrillary-tangles-B_fig3_337715716
Mahley, R. (n.d.). Apolipoprotein E4 targets mitochondria and the mitochondria-associated
membrane complex in neuropathology, including Alzheimer’s disease. ScienceDirect; Elsevier Ltd. Retrieved March 30, 2024, from https://www.sciencedirect.com/science/article/pii/S0959438823000090
Alzheimer’s disease. (n.d.). Stanfordhealthcare.org. Retrieved March 30, 2024, from https://stanfordhealthcare.org/medical-conditions/brain-and-nerves/dementia/types/alzhei mers-disease.html#:~:text=In%20healthy%20neurons%2C%20the%20tau
Huang, Y.-W. A., Zhou, B., Nabet, A. M., Wernig, M., & Südhof, T. C. (2019). Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer’s Disease Risk. The Journal of Neuroscience, 39(37), 7408–7427. https://doi.org/10.1523/JNEUROSCI.2994-18.2019
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022). ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Molecular Neurodegeneration, 17(1). https://doi.org/10.1186/s13024-022-00574-4
Hunsberger, Holly C., Pinky, Priyanka D., Smith, W., Suppiramaniam, V., & Reed, Miranda N. (2019). The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions. Neuronal Signaling, 3(2). https://doi.org/10.1042/ns20180203
Centers for Disease Control and Prevention. (2022). TBI: Get the Facts. CDC. https://www.cdc.gov/traumaticbraininjury/get_the_facts.html
American Association of Neurological Surgeons. (2019). Traumatic Brain Injury – Causes, Symptoms and Treatments. Aans.org. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Traumatic-Br ain-Injury
Classification of Traumatic Brain Injury. (n.d.). Physiopedia. https://www.physio-pedia.com/Classification_of_Traumatic_Brain_Injury
O’Neil, M., Carlson, K., & Storzbach, D. (2013, January). Complications of mild traumatic brain injury in veterans and military personnel: A Systematic Review. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK189784/table/appc.t1/
Wu, Y., Wu, H., Guo, X., Pluimer, B., & Zhao, Z. (2020). Blood–Brain Barrier Dysfunction in Mild Traumatic Brain Injury: Evidence From Preclinical Murine Models. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.01030
Agrawal, R. R., Larrea, D., Xu, Y., Shi, L., Zirpoli, H., Cummins, L. G., Emmanuele, V., Song, D., Yun, T. D., Macaluso, F. P., Min, W., Kernie, S. G., Deckelbaum, R. J., & Area-Gomez, E. (2022). Alzheimer’s-Associated Upregulation of Mitochondria-Associated ER Membranes
After Traumatic Brain Injury. Cellular and Molecular Neurobiology, 43(5), 2219–2241.
https://doi.org/10.1007/s10571-022-01299-0
Mielke, M. M., Ransom, J. E., Mandrekar, J., Turcano, P., Savica, R., & Brown, A. W. (2022).
Traumatic Brain Injury and Risk of Alzheimer’s Disease and Related Dementias in the Population. Journal of Alzheimer’s Disease: JAD, 88(3), 1049–1059. https://doi.org/10.3233/JAD-220159
Ramos-Cejudo, J., Wisniewski, T., Marmar, C., Zetterberg, H., Blennow, K., de Leon, M. J., & Fossati, S. (2018). Traumatic Brain Injury and Alzheimer’s Disease: The Cerebrovascular Link. EBioMedicine, 28, 21–30. https://doi.org/10.1016/j.ebiom.2018.01.021
Breijyeh, Z., & Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25(24), 5789. https://doi.org/10.3390/molecules25245789
Alzheimer's Association. (2019). Medical Tests for Diagnosing Alzheimer’s. Alzheimer’s Disease and Dementia; Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests
Schneider, T. (2024, February 21). Alzheimer’s blood test performs as well as FDA-approved spinal fluid tests. Washington University School of Medicine in St. Louis. https://medicine.wustl.edu/news/alzheimers-blood-test-performs-as-well-as-fda-approved -spinal-fluid-tests/#:~:text=A%20subgroup%20analysis%20of%20healthy
Sankar, R. (2024). Current and Forthcoming Treatments for Alzheimer’s Disease. Google.com. https://www.google.com/url?q=https://dpl6hyzg28thp.cloudfront.net/media/Current_and_F orthcoming_Treatments_for_Alzheimers_Disease.pdf&sa=D&source=docs&ust=1711841 811786013&usg=AOvVaw1fEhd_DrKJhXi4JD6YAwFC
Valiukas, Z., Ephraim, R., Tangalakis, K., Davidson, M., Apostolopoulos, V., & Feehan, J. (2022). Immunotherapies for Alzheimer’s Disease—A Review. Vaccines, 10(9), 1527. https://doi.org/10.3390/vaccines10091527
Three promising drugs for treating Alzheimer’s disease bring fresh hope | Alzheimer’s Society. (n.d.). Www.alzheimers.org.uk. https://www.alzheimers.org.uk/blog/three-promising-drugs-for-treating-alzheimers-diseas e-bring-fresh-hope#:~:text=What%27s%20the%20latest%20development%20with%20lec anemab%3F
Mayo Clinic. (2021, June 30). What new Alzheimer’s treatments are on the horizon? Mayo Clinic.
https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-t
reatments/art-20047780
LoBue, C., Cullum, C. M., Didehbani, N., Yeatman, K., Jones, B., Kraut, M. A., & Hart, J. (2018).
Neurodegenerative Dementias After Traumatic Brain Injury. The Journal of Neuropsychiatry and Clinical Neurosciences, 30(1), 7–13. https://doi.org/10.1176/appi.neuropsych.17070145
Downloads
Posted
Categories
License
Copyright (c) 2024 Sarina Mehta
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.