Advances in the pathogenesis of Alzheimer’s disease: A re-evaluation of the Amyloid cascade hypothesis

Leo Clinton Chukwu 1, *, John Azubuike Ekenjoku 2, Sylvester Chika Ohadoma 3, Chinedu Lawrence Olisa 4, PC Okam 4, Chidinma Cornelia Okany 1, Mansur Aliyu Ramalam 5 and Okoye Chukwuemeka Innocent 6

1 College of Medicine, Chukwuemeka Odumegwu Ojukwu University, Amaku Awka Campus Nigeria.
2 Department of Pharmacolog, College of Medicine, Abia State University, Aba Campus, Nigeria.  
3 Department of Pharmacology, College of Medical Sciences, University of Calabar, Nigeria.  
4 Department of Pharmacology, College of Medicine, Nnamdi Azikiwe University, Nnewi Campus. Nnewi Nigeria.
5 Department of Internal Medicine, Aminu Kano Teaching Hospital / Beyero University Kano.
6 Department of Medicine, Chukwuemeka Odumegwu Ojukwu University, Awka Campus Nigeria.
 
Review Article
World Journal of Advanced Research and Reviews, 2023, 17(02), 882–904
Article DOI: 10.30574/wjarr.2023.17.2.20200335
 
Publication history: 
Received on 20 October 2020; revised on 26 November 2020; accepted on 02 December 2020
 
Abstract: 
Alzheimer's disease (AD), the most common cause of dementia in the elderly is a common neurodegenerative disease characterized clinically by progressive memory deterioration. The disease becomes clinically obvious as an insidious higher intellectual function impairment with altered mood and behavior, dramatic personality changes, disorientation, declining physical coordination and inability to care for themselves. Histopathological changes including extracellular deposits of amyloid-beta (A-beta) peptides forming senile plaques (SP) and intracellular neurofibrillary tangles (NFT) of hyperphosphorylated tau in the brain. During final stages, victims are bedridden, urinary and bowel function controls may be lost with epileptic attacks. Death is usually due to pneumonia, bedsores or secondary urinary tract infections. These manifestations may indicate severe cortical dis-function. In 5-10 year time, affected individual becomes profoundly disabled, mute and immobile. Death may ensue within an average of 8 years of diagnosis, the last 3 of which are typically spent in institutions. AD is the number one cause of institutionalization in United States of America. An appraisal of the advances in pathogenesis of Alzheimer’s disease will be helpful in updating our knowledge on possible etiologies and desired advancements in therapies, clinical care and entire management. Secondly, with the rising cases of AD in tropical regions of the world and coupled with the significant scarcity of literature on Alzheimer’s Disease, the need for this compendium becomes obviously necessary, hence we chose to write. This very review derives from focused overview of pathophysiologies and management of AD. Literature searches were sourced from PubMed, Science Direct, Scopus and Google Scholar. 
 
Keywords: 
Alzheimer's disease; Amyloid-beta (A-beta) peptides; Cortical dis-function; Hyperphosphorylated tau; Intracellular neurofibrillary tangles (NFT); Senile plaques (SP)
 
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