Alzheimer’s Disease (AD) is a common form of dementia that currently affects 6.2 million Americans aged 65 and older. Data analysis predicts that this number may grow to 12.7 million by 2050. Alzheimer’s is a progressive disease that often begins with mild memory loss, but those with late-stage Alzheimer’s may lose the ability to hold a full conversation and respond to their environment. With this disease currently being the 6th leading cause of death in the United States, it is imperative that efforts to find a cure or new treatments continue to advance. Many neuroscientists have began using mouse models in their research studies, and many recent publications have shown that they have been useful in advancing Alzheimer’s-related research.
The use of neutrophic factors such as brain-derived neurotrophic factor, BDNF, has been an area of interest for AD therapy becuase the factors play a role in neural survival and neuroplasticity, meaning they could possibly fight the neurodegenerative effects of AD. A major setback of this therapy is that researchers are struggling to find a way to effectively deliver these neurotrophic factors to the brain, but one study described in the article, “Conditional BDNF Delivery from Astrocytes Rescues Memory Deficits, Spine Density, and Synaptic Properties in the 5xFAD Mouse Model of Alzheimer Disease,” has identified a new potential regulator of neurotrophic therapy using a mouse model. Researchers of this study note that astrocytes in the nervous system express low levels of BDNF, and given that astrocyte activity increases as AD progresses, these cells could possibly be genetically modified to promote neurotrophin production. When testing this possibility, they found that when BDNF was overexpressed in AD transgenic mice, they showed a significant improvement in learning and memory deficits as a result of restoration of dendritic spine density. The study also emphasizes that genetically engineered astrocytes can be advantageous for AD treatment because their delivery of BDNF is conditionally and locally administered, meaning that this treatment can be customized specifically for AD treatment.
Other neuroscientific research has utilized mouse models to identify specific genes that make individuals more susceptible to developing Alzheimer's Disease. In the article, "Systems Genetics Identifies Hp1bp3 as a Novel Modulator of Cognitive Aging," researchers identify a gene heterochromatin protein 1 binding protein 3, Hp1bp3, as a regulator of cognitive aging, one of the leading risk factors for age-related AD. They found that after genetically knocking down this protein in mice, they presented with lower memory status in comparison to control mice. Their results were further emphasized after western blotting of post mortem hippocampal tissue of cognitively impaired humans. This study suggests that developing a treatment to restore Hp1bp3 levels may be an effective treatment for AD patients.
These two studies mentioned represent only a fragment of the research efforts being made toward finding a cure and/or treatment for Alzheimer's Disease. As the research studying AD in mouse models continues, it is hopeful that the number of people affected by this disease will finally begin to decrease.
de Pins, B., Cifuentes-Díaz, C., Thamila Farah, A., López-Molina, L., Montalban, E., Sancho-Balsells, A., López, A., Ginés, S., Delgado-García, J. M., Alberch, J., Gruart, A., Girault, J.-A., & Giralt, A. (2019). Conditional BDNF delivery from astrocytes rescues memory deficits, spine density and synaptic properties in the 5xFAD mouse model of Alzheimer disease. The Journal of Neuroscience, 2441–2458. https://doi.org/10.1523/jneurosci.2121-18.2019
Neuner, S. M., Garfinkel, B. P., Wilmott, L. A., Ignatowska-Jankowska, B. M., Citri, A., Orly, J., Lu, L., Overall, R. W., Mulligan, M. K., Kempermann, G., Williams, R. W., O’Connell, K. M. S., & Kaczorowski, C. C. (2016). Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging. Neurobiology of Aging, 46, 58–67. https://doi.org/10.1016/j.neurobiolaging.2016.06.008
What is Alzheimer’s? (2021). Alzheimer’s Disease and Dementia. https://www.alz.org/alzheimers-dementia/what-is-alzheimers
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