Current Concepts of Neurodegenerative Mechanisms in Alzheimer’s Disease

Abstract

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.

Periodontitis and systemic markers of neurodegeneration: A case–control study

“…While Aβ 1‐40 is abundant and less neurotoxic, Aβ 1‐42 is less abundant and severely neurotoxic as well as more prone to aggregate to amyloid plaques (Tiwari, Atluri, Kaushik, & Yndart, ). Extracellular deposits of these Aβ peptides in brain tissue are considered as one of the key hallmarks of Alzheimer's disease (AD), which is the most common form of age‐related neurodegenerative disease (Magalingam, Radhakrishnan, Ping, & Haleagrahara, ). It has been shown that high levels of chronic inflammation measured by, for instance, acute‐phase reactants [i.e.…”

Tackling gaps in developing life‐changing treatments for dementia

“…Recent research has identified multiple neurodegenerative pathways that result in a domino-like cascade of events that eventually lead to the development of dementias. However, these changes are not seen in all cases of AD [17,18].…”

“…Recent research has identified multiple neurodegenerative pathways that result in a domino‐like cascade of events that eventually lead to the development of dementias. However, these changes are not seen in all cases of AD [17,18]. The characteristic features of AD are the pathological accumulation of extracellular plaques composed of amyloid‐β (Aβ) protein and intraneuronal tangles consisting of altered forms of tau [17].…”

“…However, these changes are not seen in all cases of AD [17,18]. The characteristic features of AD are the pathological accumulation of extracellular plaques composed of amyloid‐β (Aβ) protein and intraneuronal tangles consisting of altered forms of tau [17]. A long‐standing puzzle in AD research has been the finding that there may be a substantial number of Aβ plaques in the brain of some individuals who have otherwise normal cognition and conversely people who exhibit phenotypic AD have little or no plaque or tangle deposition [19,20].…”

Diseases Related to Types of Free Radicals

“…The antioxdant and free radicals of lipid peroxidation and cognition, and cognitive response to an exercise intervention program, in adults with coronary artery disease at risk of dementia [63]. The brain is more susceptible to lipid peroxidation due to its high oxygen consumption, high level of redox metal ions, reduced antioxidant defense mechanism, and high level of polyunsaturated fatty acids [64].…”