Amyloid Beta: The Foremost Protagonist in Alzheimer's Disease

Amyloid Beta: The Foremost Protagonist in Alzheimer's Disease

Abhinav Anand, Neha Sharma, Monica Gulati, Navneet Khurana
DOI: 10.4018/978-1-7998-3441-0.ch001
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Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is a neurodegenerative disorder (ND) that causes a progressive decline in memory and cognitive abilities. It is characterized by deposition of Aβ plaques and neurofibrillary tangles (NFTs) in the neurons, which in turn causes a decline in the brain acetylcholine levels. Aβ hypothesis is the most accepted hypothesis pertaining to the pathogenesis of AD. Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in the clearing of Aβ plaques. AD also involves impairment in UPS. The novel disease-modifying approaches involve inhibition of beta and gamma secretases. A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. This chapter deals with an overview of APP and its enzymatic cleavage leading to AD.
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AD was first described by a German neuropathologist Alois Alzheimer in 1906 (Editors of Encyclopædia Britannica, 2016). AD was recognized as the most prevalent form of dementia among geriatric persons by the commencement of 21st century. It is one of the top five most common causes of mortality in population of the United States (Centers for Disease Control and Prevention, 2017). In rare cases, it may appear in people in their 40s and 50s, but otherwise it is a disease of old age. Based on clinical, population-based studies, about 200,000 people under 65 years of age are suffering from AD. In contrast, around 5 million of those over 65 years of age have AD. As per speculations, a new case of AD is expected to be developed every 33 seconds, by 2050 (Alzheimer’s Association, 2014).

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