Glucocorticoids, synaptic plasticity and Alzheimer’s disease
Open accessAbstract
How excessive stress and cortisol exposure predispose people to clinical Alzheimer's disease (AD) is a matter of great potential medical impact. We discuss recent findings regarding the mechanism of persistent disruption of synaptic plasticity and related cognition caused by hypothalamic–pituitary–adrenal (HPA) axis dysregulation in this context. Growing evidence supports the view that in addition to the pathogenic proteins amyloid beta and tau driving HPA and hence synaptic plasticity disruption, excess glucocorticoid receptor activation promotes amyloidosis and tauopathy-mediated synaptotoxicity. The critical role of glia-mediated pro-inflammatory processes in the impairment of synaptic and cognitive function by stress is also delineated. Combining (non)-pharmacological interventions that target glucocorticoid-synaptic plasticity pathways with more classical anti-tau and anti-amyloid strategies to treat early AD prior to dementia onset certainly warrants further investigation.
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The close integration of synaptic and endocrine signaling renders the CNS particularly vulnerable to EDCs.
“This close integration of synaptic and endocrine signaling renders the CNS particularly vulnerable to EDCs, which are exogenous substances or mixtures that interfere with endocrine function and thereby cause adverse effects in exposed organisms or their offspring (Damiano et al., 2025; Gilbert et al., 2020; Klyubin et al., 2022; Schug et al., 2015).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Klyubin et al., 2022
The Introduction states that corticosterone regulates synaptic plasticity, and “Detrimental regulation of synaptic plasticity by stress and glucocorticoids” describes glucocorticoid-receptor effects on synaptic processes (page numbers unavailable). These passages support a link between endocrine and synaptic signaling, but the paper does not establish that this link makes the CNS particularly vulnerable to endocrine-disrupting chemicals (EDCs). (LLM, conf=0.84)
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Cited by
Sorted by citations
Jocsak, G., Kiss, D. S., Alymbaeva, D., Diebald, A., Zsarnovszky, A., Heinzlmann, A., & Bartha, T. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1821381 · Cited by 1 · see citing works
“…renders the CNS particularly vulnerable to EDCs, which are exogenous substances or mixtures that interfere with endocrine function and thereby cause adverse effects in exposed organisms or their offspring (Damiano et al., 2025; Gilbert et al., 2020; Klyubin et al., 2022; Schug et al., 2015).”
- Authors
- Klyubin, I., Ondrejcak, T., Hu, N.-W., & Rowan, M. J.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Klyubin, Igor
- Venue
- Current Opinion in Endocrine and Metabolic Research
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 25
- Pages
- 100365
- ISSN
- 2451-9650 (ISSN-L)
- OpenAlex
- W4281859601
- Cited by
- 16
- References
- 9
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Endocrine and Metabolic Research (publishedVersion, cc-by)
- Funders
- Health Research Board (ILP - POR -2019-051)
- Science Foundation Ireland (19/FFP/6437)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, glucocorticoids, synaptic plasticity, HPA axis dysregulation, chronic stress, cortisol, glucocorticoid receptor, amyloid-beta, tau pathology, synaptotoxicity, glial inflammation, cognitive impairment, anti-amyloid therapy, anti-tau therapy
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