Cross-Roads in Research on Neurodegenerative Diseases

Abstract

Alzheimer’s disease (AD) is the most prevalent of the neurodegenerative amyloid diseases and is characterized by accumulation of amyloid-β and tau. Recent studies have indicated that AD may be a brain infection. Although AD has not been shown to be transmissible, the burning issue is whether the potential infectious causes are the misfolded amyloid proteins themselves, or an unidentified microorganism. The idea of a replicating protein (prion) evolved from research on the transmissible spongiform encephalopathies (TSE) represented by Creutzfeldt-Jakob disease in humans. Prions are now suspect in all of the amyloid related neurodegenerative diseases. However, the popularized prion theory is controversial since there is convincing evidence that spiroplasma, a wall-less prokaryote, is involved in the pathogenesis of TSE, and may represent the trigger mechanism. Interest in bacterial involvement in AD has surfaced from discovery that most bacteria produce biofilm and that components of the biofilm experimentally induce misfolded amyloid proteins. The recent discovery of H. pylori in AD has brought this controversy to a head. In this review we will discuss involvement of bacteria as candidate causal agent/s for the neurodegenerative diseases, and relate the evidence to involvement of spiroplasma in the pathogenesis of the TSEs as a model for these neurodegenerative diseases.