Beta Amyloid Peptides: Extracellular and Intracellular Mechanisms of Clearance in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease and the most common form of dementia, characterized by the overproduction and accumulation of different amyloidβ peptide peptides (Aβ) within different areas in the brain conducting to memory loss and dementia. The Aβ cascade hypothesis of AD was originally proposed by Selkoe in 1991 by the theory that accumulation of Aβ42 is the initial trigger for neurodegeneration. The Aβ cascade hypothesis assumes that changes in the production or accumulation of Aβ are responsible for AD pathology. Different Aβ clearance mechanisms are also affected by AD pathology. Studies from the past years have revealed that the blocking of Aβ production is not effective for reducing the brain Aβ levels. However, the relevance of Aβ clearance in AD, especially in late-onset sporadic AD (LOAD), has been heightened, and the study of the Aβ clearance mechanisms has elucidated new possible therapeutic targets. This chapter summarizes recent data underlying the idea of the reduced Aβ clearance and subsequent Aβ spread in AD. We discuss the Aβ clearance mechanisms altered in AD, and the Aβ clearance through autophagy in more detail, a more recent mechanism proposed, and the new strategies to eliminate Aβ42 inducing autophagy.

Ipriflavone and Ipriflavone loaded albumin nanoparticles reverse lipopolysaccharide induced neuroinflammation in rats

“…It has been shown that the abnormal processing of APP by β and γ-secretase protease enzymes is a key event in the development of AD neuropathology [88], resulting in an increase in the generation of the Aβ42 which aggregates to form the insoluble amyloid plaques. Furthermore, the concentrations of Aβ in the brain control by their degradation by multiple amyloid-degrading enzymes (ADEs) which found to be decreased [89,90]. Insulindegrading enzyme (IDE) is a protease that degrades insulin and the β-amyloid (Aβ) peptide in the brain.…”

Age‐Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

“…Regarding prone-aggregation proteins or peptides, the beta-amyloid 1–42 peptide (the major toxic peptide observed in Alzheimer's disease) and lipofuscin have been characterized like two of the most prone-aggregation polypeptides in AMD recently. Both polypeptides have gained relevance in AMD because the burden of both increases with age, in RPE-Bruch's region, photoreceptor outer segments (POS), and retinal ganglion cells (RGCs) [ 56 , 57 ].…”

“…The presence of such peptides may serve as indicators of an impaired autophagy process in RPE cells that could involve AMD development , [ 57 , 62 ]. Therefore, preservation of the autophagic activity has been related to a lower intracellular accumulation of damaged proteins, improving RPE cell function and retarding the aging process.…”

Differential Circuit Mechanisms of Young and Aged Visual Cortex in the Mammalian Brain

“…This type of understanding will not only contribute to early detection of AD but it will also help decipher major differences between AD and other forms of dementia. Previous studies in aged mice have shown an increased deposition of AD markers such as Aβ42 peptide, microtubule-associated protein (TAU), and glial fibrillary acidic protein (GFAP) in the endothelial cells, blood vessels, and neurons of the visual cortex [107]. Furthermore, it was shown that aging could be possibly associated to the activation of the amyloidogenic pathway, which results in the overproduction and intracellular accumulation of Aβ42 in visual cortical neurons [107].…”