Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

Abstract

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in the brain and it is the main cause of dementia, which is characterized by a decline in thinking and independence in personal daily activities. AD is considered a multifactorial disease: two main hypotheses were proposed as a cause for AD, cholinergic and amyloid hypotheses. Additionally, several risk factors such as increasing age, genetic factors, head injuries, vascular diseases, infections, and environmental factors play a role in the disease. Currently, there are only two classes of approved drugs to treat AD, including inhibitors to cholinesterase enzyme and antagonists to N-methyl d-aspartate (NMDA), which are effective only in treating the symptoms of AD, but do not cure or prevent the disease. Nowadays, the research is focusing on understanding AD pathology by targeting several mechanisms, such as abnormal tau protein metabolism, β-amyloid, inflammatory response, and cholinergic and free radical damage, aiming to develop successful treatments that are capable of stopping or modifying the course of AD. This review discusses currently available drugs and future theories for the development of new therapies for AD, such as disease-modifying therapeutics (DMT), chaperones, and natural compounds.

Subcommissural Organ-Spondin-Derived Peptide Restores Memory in a Mouse Model of Alzheimer’s Disease

“…It is estimated that approximately 5.8 million people aged over 65 years are currently living with AD dementia in the United States of America ( Longhe, 2020 ). AD is a complex, multifactorial, age-related neurodegenerative disease characterized by the deposition of amyloid-beta (Aβ) peptides, formation of intracellular tau tangles and activation of other deleterious pathways (such as excitotoxicity, inflammation, oxidative stress, and synapse and neurovascular dysfunctions), which impede neuronal function and, ultimately, lead to neuronal death and cognitive decline ( Heneka et al, 2015 ; Bejanin et al, 2017 ; Kisler et al, 2017 ; Tönnies and Trushina, 2017 ; Wang and Reddy, 2017 ; Jackson et al, 2019 ; Breijyeh and Karaman, 2020 ; Ayton and Bush, 2021 ). The current standards of care for the treatment of AD include therapies targeting the disturbances of the cholinergic and glutamatergic systems using drugs, such as donepezil (Aricept ® ), a reversible acetylcholinesterase inhibitor, and memantine (Ebixa ® ), an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, or a combination of these agents (Namzaric ® ) ( Ferreira-Vieira et al, 2016 ; Arvanitakis et al, 2019 ; Conway, 2020 ).…”

“…This represents a major limitation in the attempt to reduce the rate of progression of AD pathology, which is necessary to reduce functional and cognitive deficits that result from AD. Therefore, efforts have been made to develop effective therapeutics at preclinical and clinical stages; among these, almost 30 anti-amyloid and anti-tau agents are in phase 3 ( Breijyeh and Karaman, 2020 ; Haake et al, 2020 ; Zhang et al, 2020 ).…”

Central Administration of Ampelopsin A Isolated from Vitis vinifera Ameliorates Cognitive and Memory Function in a Scopolamine-Induced Dementia Model

“…Alzheimer’s disease (AD) is the most common neurodegenerative disease with progressive memory loss and cognitive decline in the elderly [ 1 ]. The pathological hallmarks of AD include amyloid-β protein accumulation, tau protein aggregation, excessive oxidative stress, and cholinergic dysfunction [ 2 ]. Cholinergic circuits have been implicated in cognitive functioning, especially in hippocampus-dependent memory formation, through the modulation of hippocampal synaptic plasticity and transmission [ 3 ].…”

Medicinal plants effective against alzheimer’s disease: An update

“…Chronic neurodegeneration leading to Alzheimer's disease (AD) has become a major health challenge affecting over 50 million people globally with a prediction to reach 152 million by 2050. 3 Multiple factors are responsible for neuronal damage including oxidative stress and accumulation of the amyloid β (Aβ) protein in the brain. However, the biggest challenge here is in its treatment.…”