Altered expression of costimulatory molecules in dementias

Area of Science:

• Immunology
• Neuroscience
• Gerontology

Background:

• Co-stimulatory molecules are crucial for immune responses.
• Their regulation in neurodegenerative diseases like dementia is poorly understood.
• T-cell mediated immunity may play a role in dementia pathogenesis.

Purpose of the Study:

• To investigate the expression of CD28, ICOS (CD278), and CTLA-4 (CD152) on T cells in patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD).
• To compare T-cell co-stimulatory molecule expression in dementia patients with non-demented elderly controls.
• To explore correlations between T-cell markers, cognitive function, and disease biomarkers.

Main Methods:

• Flow cytometry was used to quantify CD28, ICOS, and CTLA-4 expression on CD4+ and CD8+ T cells in peripheral blood.
• Patient cohorts included MCI (N=19), AD (N=51), VD (N=21), FTD (N=6), and controls (N=19).
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE); cerebrospinal fluid (CSF) biomarkers (tau, Amyloid-β) and blood-CSF-barrier markers (Q Albumin) were analyzed.

Main Results:

• CD28 and ICOS expression remained unchanged in AD, FTD, and VD patients compared to controls.
• Increased CTLA-4 expression was observed on CD4+ T cells in AD and FTD patients, and on CD8+ T cells in VD patients.
• In AD, declining CD28 and increasing CTLA-4 correlated with cognitive decline and CSF biomarkers.
• FTD patients showed associations between Q Albumin, CD28, and ICOS expression.

Conclusions:

• T-cell co-stimulatory molecule expression, particularly CTLA-4, is dysregulated in dementia, especially in AD.
• This immune imbalance may contribute to chronic inflammation and disease progression in dementia.
• Further research is warranted to explore the therapeutic potential of modulating T-cell responses in neurodegenerative diseases.