Beta Amyloid Peptides: Extracellular And Intracellular Mechanisms Of Clearance In Alzheimer'S Disease

Alzheimer's disease (AD) is a neurodegenerative disease and the most common form of dementia, characterized by the overproduction and accumulation of different amyloid-beta peptide peptides (A beta) within different areas in the brain conducting to memory loss and dementia. The A beta cascade hypothesis of AD was originally proposed by Selkoe in 1991 by the theory that accumulation of A beta 42 is the initial trigger for neurodegeneration. The A beta cascade hypothesis assumes that changes in the production or accumulation of A beta are responsible for AD pathology. Different A beta clearance mechanisms are also affected by AD pathology. Studies from the past years have revealed that the blocking of A beta production is not effective for reducing the brain A beta levels. However, the relevance of A beta clearance in AD, especially in late-onset sporadic AD (LOAD), has been heightened, and the study of the A beta clearance mechanisms has elucidated new possible therapeutic targets. This chapter summarizes recent data underlying the idea of the reduced A beta clearance and subsequent A beta spread in AD. We discuss the A beta clearance mechanisms altered in AD, and the A beta clearance through autophagy in more detail, a more recent mechanism proposed, and the new strategies to eliminate A beta 42 inducing autophagy.