Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer's Disease

Area of Science:

• Neuroscience
• Immunology
• Microbiology

Background:

• Alzheimer's disease (AD) is the leading cause of dementia globally, with largely unknown etiology.
• The amyloid cascade hypothesis, involving amyloid-beta plaques and tau tangles, is the dominant explanation.
• Emerging evidence supports an infection hypothesis, linking microbial involvement to dementia development.

Purpose of the Study:

• To explore the infection hypothesis as a potential cause of Alzheimer's disease.
• To investigate the role of microbial infections and the innate immune system in AD pathogenesis.
• To identify potential new therapeutic targets based on the infection hypothesis.

Main Methods:

• Review of experimental and epidemiological data supporting microbial involvement in dementia.
• Analysis of the proposed mechanism where infections precede amyloid-beta plaque formation.
• Examination of the antimicrobial properties of amyloid-beta and its role in disease progression.

Main Results:

• Infections, directly or via virulence factors, may precede amyloid-beta plaque formation.
• Amyloid-beta's antimicrobial role may shift from beneficial to detrimental as the disease progresses.
• Infection triggers neuroinflammation and systemic inflammation, leading to neurodegeneration and immune cell senescence.

Conclusions:

• Microbial sources from gut, oral, nasal, and skin microbiomes are implicated in AD.
• The infection hypothesis provides a new framework for understanding AD.
• Potential therapies include targeting infections, modulating the immune system, or altering host metabolism.