Spike Protein Fragments Promote Alzheimer’s Amyloidogenesis

• Published in: ACS applied materials & interfaces Vol. 15; no. 34; pp. 40317 - 40329
• Main Authors: Cao, Sujian, Song, Zhiyuan, Rong, Jinyu, Andrikopoulos, Nicholas, Liang, Xiufang, Wang, Yue, Peng, Guotao, Ding, Feng, Ke, Pu Chun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 30-08-2023
• Subjects: Aged; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Animals; Biological and Medical Applications of Materials and Interfaces; COVID-19; Humans; Pandemics; Peptide Fragments - metabolism; Post-Acute COVID-19 Syndrome; SARS-CoV-2 - metabolism; Spike Glycoprotein, Coronavirus; Virus Diseases; Zebrafish - metabolism; SARS-CoV-2; Alzheimer’s disease; amyloid β; virus; spike protein
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.3c09815

Alzheimer’s disease (AD) is a major cause of dementia inducing memory loss, cognitive decline, and mortality among the aging population. While the amyloid aggregation of peptide Aβ has long been implicated in neurodegeneration in AD, primarily through the production of toxic polymorphic aggregates and reactive oxygen species, viral infection has a less explicit role in the etiology of the brain disease. On the other hand, while the COVID-19 pandemic is known to harm human organs and function, its adverse effects on AD pathobiology and other human conditions remain unclear. Here we first identified the amyloidogenic potential of 1058HGVVFLHVTYV1068, a short fragment of the spike protein of SARS-CoV-2 coronavirus. The peptide fragment was found to be toxic and displayed a high binding propensity for the amyloidogenic segments of Aβ, thereby promoting the aggregation and toxicity of the peptide in vitro and in silico, while retarding the hatching and survival of zebrafish embryos upon exposure. Our study implicated SARS-CoV-2 viral infection as a potential contributor to AD pathogenesis, a little explored area in our quest for understanding and overcoming Long Covid.