EXPLORING EMERGING THERAPEUTIC APPROACHES FOR ALZHEIMER'S DISEASE: A FOCUS ON TARGETING NEUROINFLAMMATION AND MOLECULAR PATHWAYS

Main Article Content

Qurat-Ul-Ain Bhutto
Qamreen
Dr. Adut Matik
Stephen Matthew Chui
Mr. V. Sampath
Hameed Ullah

Keywords

Alzheimer's Disease, Neuroinflammation, Molecular Pathways, Therapeutic Approaches, Cholinergic Hypothesis, Glutamatergic Dysfunction, Amyloid-Beta Cascade

Abstract

Introduction: Alzheimer's disease (AD) is an irreversible neurodegenerative condition marked by cerebral cortical atrophy resulting from the accumulation of beta-amyloid (βA) plaques and neurofibrillary tangles (NFTs). With an alarming global prevalence, estimated at 55 million in 2019 and projected to reach 139 million by 2050, the disease's impact is escalating. This review provides a comprehensive overview of AD, delving into its historical background, clinical manifestations, and the burgeoning significance of neuroinflammation.


Methodology: A literature review was conducted utilizing articles from PubMed, SciELO, and Science databases to compile a comprehensive understanding of AD, emphasizing the role of neuroinflammation.


Molecular Bases: The cholinergic hypothesis, glutamatergic dysfunction, amyloid-beta cascade, oligomeric hypothesis, metallic hypothesis, and tau hypothesis collectively shape our molecular understanding of AD. Despite advancements in pharmacological interventions, questions persist about the natural history and treatment efficacy, particularly in addressing cognitive decline.


Neuroinflammation: The neuroinflammatory process in AD, initiated by microglia and astrocytes responding to βA plaque and tau protein accumulation, is a pivotal aspect of disease progression. Microglial cells, initially beneficial, transform into a neurotoxic force as the disease advances. Astrocytes also display dual roles, offering neuroprotection in early stages but turning pro-inflammatory in advanced stages.


Anatomophysiological Correlation: The anatomical impact of AD unfolds in a temporal-parietal-frontal course, affecting the medial temporal lobe, including the entorhinal cortex and hippocampus. This progression, intertwined with the limbic system, results in atrophy, episodic memory deficits, and cognitive dysfunction. Imaging modalities such as MRI reveal key anatomical changes associated with disease progression.


Anatomical-Imaginological Correlation: MRI findings, including atrophy of temporal lobes and hippocampus, ventricular enlargement, and cortical sulci widening, offer crucial diagnostic insights. The correlation between anatomical changes and neuroinflammation becomes evident, emphasizing the interplay between structural alterations and disease severity.


Discussion: Neuroimaging tests play a pivotal role in diagnosing AD, relying on volumetric changes in key brain regions. Neuropathological findings underscore neuronal loss, glial cell activation, and the intricate relationship between inflammation and central nervous system degeneration.


Conclusion: In conclusion, neuroinflammation, triggered by βA plaque formation and tau protein accumulation, emerges as a central feature in AD. The interconnection between anatomical changes and neuroinflammation holds significant diagnostic and prognostic value, contributing to a comprehensive understanding of disease evolution and facilitating clinical applications. Further research is essential to unravel the complexities of AD and develop targeted therapeutic interventions


 

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