Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer's disease

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Alzheimer's disease (AD) and vascular dementia (VaD) are complex neurodegenerative conditions.
• The role of systemic infections and associated brain changes in dementia progression is not fully understood.
• Cerebral vascular function and cytokine profiles are altered in dementia.

Purpose of the Study:

• To investigate the impact of systemic infection on brain cytokine levels and cerebral vascular function in AD and VaD.
• To compare these effects across different stages of dementia and in non-dementia controls.
• To determine the relationship between systemic infection, brain changes, and dementia severity.

Main Methods:

• Analysis of superior temporal cortex tissue from AD patients, VaD patients, and age-matched controls.
• Measurement of brain cytokine levels using Mesoscale Discovery Multiplex Assays.
• Assessment of cerebrovascular function markers (e.g., MAG:PLP1, VEGF, fibrinogen) via ELISA.

Main Results:

• Elevated brain cytokines (e.g., IL-15, IL-17A) were observed in AD and VaD, with specific patterns related to disease stage.
• Systemic infection further increased specific cytokines (e.g., IL-1β, IL-6, TNF-α) in AD patients.
• Cerebral hypoperfusion and blood-brain barrier leakiness were exacerbated by systemic infection in all groups, independent of amyloid-β42 levels.

Conclusions:

• Systemic infection significantly contributes to neuroinflammation and exacerbates cerebrovascular dysfunction in AD and VaD.
• These effects occur independently of insoluble amyloid-β levels.
• Early identification and management of systemic infections are critical for mitigating dementia progression in the elderly.