[Alzheimer's disease: the infectious hypothesis]

Area of Science:

• Neuroscience
• Pathology
• Infectious Diseases

Background:

• Alzheimer's disease (AD) pathogenesis remains incompletely understood, with the amyloid cascade hypothesis being prominent but lacking full mechanistic clarity.
• Key pathological hallmarks of AD include amyloid-beta (Aß) peptide deposition, tau protein degeneration, and neuronal loss.
• Alterations in blood-brain barrier integrity and neuroinflammation are increasingly recognized as crucial factors in AD progression, particularly affecting Aß clearance.

Purpose of the Study:

• To review existing epidemiological and experimental evidence regarding the potential role of infectious agents in Alzheimer's disease (AD) pathogenesis.
• To explore how infectious agents might contribute to neurodegeneration, Aß deposition, and tau pathology.
• To assess the impact of systemic inflammation and specific pathogens on AD development.

Main Methods:

• Review of epidemiological studies and experimental research on cellular and murine models.
• Examination of data related to herpes simplex virus (HSV), spirochetes, Chlamydia pneumoniae, Borrelia, and systemic inflammation.
• Consideration of Aß peptide and tau protein as potential prion-like agents.

Main Results:

• Evidence suggests infectious agents, including viruses and bacteria, may play a role in AD through direct neurotropism or by exacerbating systemic inflammation.
• Impaired Aß peptide clearance, linked to blood-brain barrier dysfunction and neuroinflammation, points towards a potential contribution of infections.
• The possibility of Aß peptide and tau protein exhibiting prion-like behavior is considered in the context of infectious influences.

Conclusions:

• Infectious agents represent a potential contributing factor to Alzheimer's disease (AD) pathology, influencing neurodegeneration via neuroinflammation and altered Aß clearance.
• While current evidence is not conclusive, the reviewed studies highlight the need for further investigation into the interplay between infections and AD.
• Understanding the impact of infectious agents may offer novel therapeutic targets for Alzheimer's disease.