Proinflammatory cytokines, sickness behavior, and Alzheimer disease

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Systemic inflammation in Alzheimer disease (AD) is linked to delirium and sickness behavior.
• Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6), mediate immune-to-brain communication.
• Sickness behavior encompasses centrally mediated symptoms arising from systemic inflammation, independent of delirium.

Purpose of the Study:

• To investigate the association between elevated serum TNFα or IL-6 and sickness behavior symptoms in AD patients.
• To determine if this association persists independently of delirium development.
• To examine these relationships in a prospective cohort of individuals with mild to severe AD.

Main Methods:

• A prospective cohort study involving 300 subjects with mild to severe AD.
• Baseline cognitive assessments and blood samples for inflammatory markers (TNFα, IL-6, CRP).
• Repeated cognitive assessments (including delirium detection) and blood sampling at 2, 4, and 6 months, with independent carer interviews for neuropsychiatric symptoms.

Main Results:

• Raised serum TNFα and IL-6 levels were associated with a roughly 2-fold increase in the frequency of sickness behavior symptoms.
• C-reactive protein (CRP) levels did not show a significant association with sickness behavior.
• The observed relationships between TNFα/IL-6 and sickness behavior were independent of delirium presence.

Conclusions:

• Elevated serum proinflammatory cytokines (TNFα, IL-6) are significantly associated with sickness behavior symptoms in Alzheimer disease.
• These findings highlight the role of systemic inflammation in the manifestation of common neuropsychiatric features in AD.
• The association between proinflammatory cytokines and sickness behavior is independent of delirium, suggesting a distinct pathway.