Contribution of Multivesicular Bodies to the Prion-Like Propagation of Lesions in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a chronic developing dementing disease characterized by coexistence of two types of lesions, the parenchymal amyloid deposits and the intraneuronal neurofibrillary tangles. Amyloid deposits are composed of amyloid-beta peptides that derive from sequential cleavages of its precursor named amyloid protein precursor (APP). Neurofibrillary tangles (NFT) results from intraneuronal aggregation of abnormally modified microtubule-associated Tau proteins. A synergistic relationship between the two lesions may trigger the progression of the disease. Thus, starting in the entorhinal cortex and slowly progressing through temporal, frontal, parietal and occipital cortex, the progression of NFT is well correlated with clinical expression of the disease. However, little is known about the mechanism underlying spatiotemporal propagation of these lesions ultimately leading to the disease. A growing number of studies suggest a prion-like diffusion of amyloid deposits and NFT, which could even be extrapolate to several other neurodegenerative diseases. In the present chapter, we will develop the current hypotheses regarding the molecular and cellular mechanisms driving the development and spreading of Alzheimer’s disease lesions involving multivesicular bodies.