Chapter 11: Transmission of Pathogenic Proteins and the Role of Microbial Infection in Alzheimer's Disease Pathology Check Access

Alzheimer's disease (AD) is characterized by misfolding of Aβ and tau to form neurotoxic aggregation species that trigger neurodegeneration in the brain. These toxic proteins behave similarly to prions capable of spreading in the brain, acting as seed and template to generate more aggregation species, which contribute to the propagation of AD pathology. The pathogenic proteins spread between cells, different regions within the brain and recent evidence also shows human-to-human transmission. The multifactorial nature has compelled researchers to propose and pursue various hypotheses to describe the pathological routes of AD. Almost three decades ago an infectious hypothesis was proposed that highlighted the evidence of microbial infections in the AD brain and its role in pathogenesis. This revelation was ignored for years, while recent studies have demonstrated the association of viral and bacterial infection with AD. In this chapter, we discuss different mechanisms involved in transcellular transmission of Aβ and tau, spread and deposition pattern of proteins within the brain, the different mechanisms involved and the spreading models to explain the transmission process. Iatrogenic human-to-human transmission of AD pathology and its implication is discussed. In line with infectious hypothesis, the controversial role of virus and bacteria in AD pathology, their disease-causing mechanisms and implications in managing AD are addressed.