| Sure! Here's the output from the video-- The understanding of amyloid-beta's role in Alzheimer's disease has evolved significantly over time:
Initially, amyloid plaques were considered the primary cause of Alzheimer's, leading to the amyloid cascade hypothesis (Fantini2020Progress pages 4-7).
Research shifted focus from plaques to small oligomeric structures of amyloid-beta as the neurotoxic culprits (Fantini2020Progress pages 4-7).
It was discovered that physiological (low) levels of amyloid-beta enhance memory, while only pathological (high) levels are harmful (Morley2014The pages 1-6).
The view changed from Aβ peptides being purely harmful to recognizing their important physiological functions in the brain (Fantini2020Progress pages 1-4).
Clinical trials targeting amyloid have had mixed results, leading to questioning of the amyloid hypothesis (Hardy2009The pages 2-3).
Some researchers now propose rejecting the amyloid cascade hypothesis as insufficient to explain Alzheimer's complex biology (Herrup2015The pages 1-1).
There's growing recognition that tau pathology may correlate better with cognitive impairment than amyloid accumulation (Mullane2020Alzheimer's pages 16-16).
Current approaches are shifting towards considering amyloid-beta as one factor among many in the aging process, rather than the central cause of Alzheimer's (Josepha2001Copernicus pages 1-2). References:
Fantini2020Progress: Jacques Fantini, Henri Chahinian, and Nouara Yahi. Progress toward alzheimer’s disease treatment: leveraging the achilles’ heel of aβ oligomers? Protein Science, 29(8):1748–1759, July 2020. URL: http://dx.doi.org/10.1002/pro.3906, doi:10.1002/pro.3906. This article has 48 citations and is from a peer-reviewed journal. Morley2014The: John E. Morley and Susan A. Farr. The role of amyloid-beta in the regulation of memory. Biochemical Pharmacology, 88(4):479–485, April 2014. URL: http://dx.doi.org/10.1016/j.bcp.2013.12.018, doi:10.1016/j.bcp.2013.12.018. This article has 96 citations and is from a domain leading peer-reviewed journal. Hardy2009The: John Hardy. The amyloid hypothesis for alzheimer’s disease: a critical reappraisal. Journal of Neurochemistry, 110(4):1129–1134, July 2009. URL: http://dx.doi.org/10.1111/j.1471-4159.2009.06181.x, doi:10.1111/j.1471-4159.2009.06181.x. This article has 615 citations and is from a domain leading peer-reviewed journal. Josepha2001Copernicus: J Josepha. Copernicus revisited: amyloid beta in alzheimer’s disease. Neurobiology of Aging, 22(1):131–146, January 2001. URL: http://dx.doi.org/10.1016/s0197-4580(00)00211-6, doi:10.1016/s0197-4580(00)00211-6. This article has 146 citations and is from a domain leading peer-reviewed journal. Hamley2012The: I. W. Hamley. The amyloid beta peptide: a chemist’s perspective. role in alzheimer’s and fibrillization. Chemical Reviews, 112(10):5147–5192, July 2012. URL: http://dx.doi.org/10.1021/cr3000994, doi:10.1021/cr3000994. This article has 775 citations and is from a highest quality peer-reviewed journal. Herrup2015The: Karl Herrup. The case for rejecting the amyloid cascade hypothesis. Nature Neuroscience, 18(6):794–799, May 2015. URL: http://dx.doi.org/10.1038/nn.4017, doi:10.1038/nn.4017. This article has 593 citations and is from a highest quality peer-reviewed journal. Jacobs2022It’s: Noortje Jacobs and Bert Theunissen. It’s groundhog day! what can the history of science say about the crisis in alzheimer’s disease research? Journal of Alzheimer’s Disease, 90(4):1401–1415, December 2022. URL: http://dx.doi.org/10.3233/jad-220569, doi:10.3233/jad-220569. This article has 4 citations. Mullane2020Alzheimer’s: Kevin Mullane and Michael Williams. Alzheimer’s disease beyond amyloid: can the repetitive failures of amyloid-targeted therapeutics inform future approaches to dementia drug discovery? Biochemical Pharmacology, 177:113945, July 2020. URL: http://dx.doi.org/10.1016/j.bcp.2020.113945, doi:10.1016/j.bcp.2020.113945. This article has 68 citations and is from a domain leading peer-reviewed journal. |