The Interplay Between Cholesterol and Amyloid-β on HT22 Cell Viability, Morphology, and Receptor Tyrosine Kinase Signaling

Morgan J. Robinson, Sean Newbury, Kartar Singh, Zoya Leonenko, Michael A. Beazely, Rakez Kayed

Research output: Contribution to journalArticlepeer-review


Background: There is a lack of understanding in the molecular and cellular mechanisms of Alzheimer's disease that has hindered progress on therapeutic development. The focus has been on targeting toxic amyloid-β (Aβ) pathology, but these therapeutics have generally failed in clinical trials. Aβ is an aggregation-prone protein that has been shown to disrupt cell membrane structure in molecular biophysics studies and interfere with membrane receptor signaling in cell and animal studies. Whether the lipid membrane or specific receptors are the primary target of attack has not been determined. Objective: This work elucidates some of the interplay between membrane cholesterol and Aβ42 on HT22 neuronal cell viability, morphology, and platelet-derived growth factor (PDGF) signaling pathways. Methods: The effects of cholesterol depletion by methyl-β-cyclodextrin followed by treatment with Aβ and/or PDGF-AA were assessed by MTT cell viability assays, western blot, optical and AFM microscopy. Results: Cell viability studies show that cholesterol depletion was mildly protective against Aβ toxicity. Together cholesterol reduction and Aβ42 treatment compounded the disruption of the PDGFα receptor activation. Phase contrast optical microscopy and live cell atomic force microscopy imaging revealed that cytotoxic levels of Aβ42 caused morphological changes including cell membrane damage, cytoskeletal disruption, and impaired cell adhesion; cell damage was ameliorated by cellular cholesterol depletion. Conclusions: Cholesterol depletion impacted the effects of Aβ42 on HT22 cell viability, morphology, and receptor tyrosine kinase signaling.

Original languageEnglish (US)
Pages (from-to)1663-1683
Number of pages21
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - Dec 6 2023


  • Alzheimer's disease
  • HT22 cells
  • amyloid-β
  • atomic force microscopy
  • cholesterol
  • platelet-derived growth factor
  • receptor tyrosine kinase

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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