Convergent effects of glucocorticoid stress hormones and amyloid beta in human primary olfactory neuroepithelial

ABSTRACT: Stressful life events and glucocorticoid (stress) hormones appear to increase risk of Alzheimer’s disease and hasten its progression, but the reasons for this remain unclear. One contributor may be intracellular interactions between amyloid β (Aβ), an early pathological hallmark of Alzheimer’s disease, and glucocorticoids in which 1) glucocorticoids influence Aβ-related cellular pathology and/or Aβ production, and 2) Aβ alters glucocorticoid signaling. To explore both aspects of this possible relationship, the present study investigated whether glucocorticoids and Aβ have overlapping or synergistic effects on the cellular proteome, and whether Aβ influences intracellular glucocorticoid signalling. Olfactory neuroepithelium-derived (ONe) cells from six adult human donors were cultured in vitro and treated with soluble Aβ40 or Aβ42, followed by glucocorticoids (dexamethasone or cortisol). ONe cell treatment with Aβ40 or Aβ42 induced striking proteomic changes in biological processes including innate immunity and mitochondrial function. ONe cells revealed overlapping impacts of Aβ and glucocorticoids, in which- fifteen proteins were significantly altered by both treatments. For twelve of these proteins (seven of which were mitochondrial proteins) dexamethasone counteracted the effects of Aβ. Consistent with these findings, Aβ40 increased, but dexamethasone decreased, ONe cell proliferation. Aβ did not influence intracellular glucocorticoid receptor translocation but there was evidence that some proteins, including complement C3, may be selectively dysregulated by a combination of Aβ and dexamethasone. Overall, this study revealed overlapping effects of glucocorticoids and Aβ, highlighting the potential that glucocorticoid signaling in neurons may counteract some effects of soluble Aβ and exacerbate others inside neurons in ageing and Alzheimer’s disease

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Richard Wilson  

LAB HEAD: Dr Richard Wilson

PROVIDER: PXD056362 | Pride | 2026-06-29

REPOSITORIES: Pride