Alzheimer’s at the Genetic Level

Medical treatments are shifting from broad approaches to precise genetic targeting, especially for finicky diseases like Alzheimer's dementia. While many past efforts focused on amyloid β plaques, new research is exploring genetic regulators like APP, which influences amyloid levels, and KDM5, an enzyme linked to memory and cognition. Clinical trials are testing drugs that could balance these proteins and potentially slow cognitive decline at its root. Tune in this week for a deep look into the genetics of Alzheimer'sShare with a friend. Rate, Review, and Subscribe to MedEvidence! Articles to be notified when new episodes are released.Follow us on Social Media:FacebookInstagramTwitterLinkedInTiktokYoutubeFor more great content, including discussions by physicians and clinical research experts, check out the MedEvidence! podcast. www.MedEvidence.comThank you for listening!References:Bandyopadhyay, S., & Rogers, J. T. (2014). Alzheimer's disease therapeutics targeted to the control of amyloid precursor protein translation: maintenance of brain iron homeostasis. Biochemical pharmacology, 88(4), 486-494. https://pmc.ncbi.nlm.nih.gov/articles/PMC4064675/Kim, C. K., et al. (2022). Alzheimer’s disease: key insights from two decades of clinical trial failures. Journal of Alzheimer's Disease, 87(1), 83-100. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215699Maccecchini, M. L., et al. (2012). Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans. Journal of Neurology, Neurosurgery & Psychiatry, 83(9), 894-902. https://jnnp.bmj.com/content/83/9/894.shortDelport, A., & Hewer, R. (2022). The amyloid precursor protein: A converging point in Alzheimer’s disease. Molecular Neurobiology, 59(7), 4501-4516. https://link.springer.com/article/10.1007/s12035-022-02863-xCahill, C. M., et al. (2009). Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Biochimica et Biophysica Acta (BBA)-General Subjects, 1790(7), 615-628. https://pmc.ncbi.nlm.nih.gov/articles/PMC3981543/Kisby, B., et al. (2019). Alzheimer’s disease and its potential alternative therapeutics. Journal of Alzheimer's disease & Parkinsonism, 9(5). https://pmc.ncbi.nlm.nih.gov/articles/PMC6777730/Collins, B. E., et al. (2019). Broad domains of histone 3 lysine 4 trimethylation are associated with transcriptional activation in CA1 neurons of the hippocampus during memory formation. Neurobiology of learning and memory, 161, 149-157. https://pmc.ncbi.nlm.nih.gov/articles/PMC6541021/Kandel, E. R., et al (Eds.). (2000). Principles of neural science (Vol. 4). New York: McGraw-hill.Gehling, V. S., et al. (2016). Identification of potent, selective KDM5 inhibitors. Bioorganic & medicinal chemistry letters, 26(17), 4350-4354. https://www.sciencedirect.com/science/article/abs/pii/S0960894X16307399Liu, X., & Secombe, J. (2015). The histone demethylase KDM5 activates gene expression by recognizing chromatin context through its PHD reader motif. Cell reports, 13(10), 2219-2231. https://pmc.ncbi.nlm.nih.gov/articles/PMC4684901/Zhou, J. (2022). Gene-expression control in early and late-onset dementia. [Doctoral dissertation, Georg-August-Universität Göttingen]. http://dx.doi.org/10.53846/goediss-9465Share with a friend. Rate, Review, and Subscribe to MedEvidence! Articles to be notified when new episodes are released.Follow us on Social Media:FacebookInstagramTwitterLinkedInTiktokYoutubeFor more great content, including discussions by physicians and clinical research experts, check out the MedEvidence! Podcast and MedEvidence.comThank you for listening!