Support for the Amyloid Cascade Hypothesis in Guiding Further Avenues of Treatment in Alzheimer's Disease

Alzheimer’s disease currently affects 50 million individuals and is expected to increase to 152 million by 2050. Despite this prevalence, the neurodegenerative disease still has minimal treatments, and there are minimally FDA approved drugs that show any slowing in cognitive decline. One of these drugs, aducanumab (Aduhelm), attacks the amyloid-beta plaques that form in Alzheimer’s. This evidence coincides with the predominant theory in Alzheimer’s pathogenesis, the Amyloid Cascade Hypothesis (ACH). However, there are conflicting reports about whether evidence supporting aducanumab warranted FDA approval. Some scientists suggest that the underlying pathology of Alzheimer’s is via tau, which involves the accumulation of neurofibrillary tau tangles that progress to the disease’s diagnostic lesions. To determine if degrading amyloid plaques is the most beneficial path of treatment, a comprehensive literature review of current Alzheimer’s research and understanding of how the disease is treated was conducted. This review found that the ACH should remain the prevailing theory based on Alzheimer’s progression, with findings that indicate amyloid plaques are necessary to induce the phosphorylation crucial to the development of tau tangles. This data suggests that Alzheimer’s disease develops via an amyloid-induced tau-pathology. In addition, a multitude of other treatments has been shown to reduce these plaques along with aducanumab, which renews promise in using the ACH to develop treatments. Using the ACH as a guide and implementing the treatments listed in this paper, new drugs like aducanumab target the perpetrator of Alzheimer’s and may stop or reverse progression to more severe presentations of the disease.

Abbreviations: ACH – Amyloid Cascade Hypothesis; Aβ – amyloid-beta; AD – Alzheimer’s Disease; NFT – neurofibrillary tangle

Keywords: Aβ plaque; aducanumab; neurofibrillary tau tangle; neurotoxicity; pathogenesis; peptide

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