Alicia Kwan Su Huey

Title: The Skin-Brain Axis: Exploring Neuroinflammation’s Role in Dermatological and Neurological Disorders

Abstract

Background: The skin–brain axis describes bidirectional neuroimmune communication whereby psychological stress can amplify cutaneous inflammation and, conversely, chronic inflammatory skin disease can influence central nervous system (CNS) function. Psoriasis has been increasingly associated with later-life cognitive decline and Alzheimer’s disease (AD), potentially through shared inflammatory pathways.

Aim: To synthesise mechanistic links between psoriasis and AD across neuroendocrine and immune pathways, and to summarise emerging diagnostic and therapeutic implications.

Methods: Narrative review of peer-reviewed English-language literature identified via PubMed, Scopus, Web of Science, ScienceDirect and Google Scholar using terms relating to psoriasis, AD, neuroinflammation, cytokines, the hypothalamic–pituitary–adrenal (HPA) axis, blood–brain barrier (BBB), biomarkers and artificial intelligence (AI).

Results: Stress-mediated activation of the HPA axis and neuropeptides (e.g., corticotropin-releasing hormone, cortisol and substance P) modulates keratinocyte, mast-cell and T-cell activity, sustaining psoriatic inflammation. Systemic cytokines central to psoriasis—IL-17, IL-23, TNF-α and IL-6—are also implicated in AD-associated neuroinflammation and may contribute to BBB dysfunction, with downstream microglial and astrocyte activation. Shared cardiometabolic comorbidities (obesity, type 2 diabetes, hypertension and dyslipidaemia) may further amplify systemic inflammatory burden and accelerate cognitive decline. Therapeutic overlap is emerging: biologics targeting TNF-α or IL-17 and agents modulating JAK-STAT signalling may attenuate inflammatory crosstalk across skin and CNS compartments. Diagnostic innovation includes exploration of skin-based detection of pathological protein signatures and AI-assisted phenotyping to support personalised risk stratification.

Conclusion: Converging neuroendocrine and cytokine-driven mechanisms support a biologically plausible psoriasis–AD link. Prospective longitudinal studies are needed to clarify causality, validate clinically actionable biomarkers and determine whether systemic anti-inflammatory treatment modifies long-term cognitive outcomes.