Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aβ, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD.

In vivo two-photon FLIM imaging to investigate metabolism in live animals

“…The loss of cognitive functions such as thinking, behavior, emotion as well as memory, is defined as dementia [1]. Currently 55 million people worldwide suffering with dementia which is set to rise to 139 million by 2050 [2].…”

American Ginseng for the Treatment of Alzheimer’s Disease: A Review

“…Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder primarily affecting the elderly population. Presently, approximately 35 million individuals worldwide are impacted by this disease, and it is projected to rise to 70 million by 2030, with China accounting for approximately 30% of the cases [26][27][28]. The clinical manifestations of AD encompass progressive memory loss, cognitive dysfunction, behavioral abnormalities, and profound social impairment, ultimately resulting in fatality [29].…”

Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer’s disease by promoting synaptic plasticity of adult-born granule cells

“…Alzheimer’s disease (AD) is an increasingly prevalent condition in the context of global aging and has emerged as a leading cause of death among the elderly, imposing a substantial economic burden worldwide. AD is characterized by extracellular deposition of amyloid-β (Aβ), intracellular hyperphosphorylated tau-containing neurofibrillary tangles, synaptic loss and neuronal death [ 1 ]. While the deposition of Aβ was previously considered to be the primary cause of AD-related cognitive impairment, recent evidence suggests that cognitive impairment occurs before the appearance of extracellular Aβ-containing senile plaques in the mouse model for AD and patients with mild cognitive impairmen [ 2 – 4 ].…”