Pathophysiological Aspects and Therapeutic Armamentarium of Alzheimer’s Disease: Recent Trends and Future Development

• Published in: Cellular and molecular neurobiology 2023-11, Vol.43 (8), p.3847-3884
• Main Authors: Dave, Bhavarth P., Shah, Yesha B., Maheshwari, Kunal G., Mansuri, Kaif A., Prajapati, Bhadrawati S., Postwala, Humzah I., Chorawala, Mehul R.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - metabolism; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Cell Biology; Cell death; Cholinesterase Inhibitors; Dementia; Dementia disorders; Dendrimers - metabolism; Dendrimers - therapeutic use; Epigenetics; Gene therapy; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Humans; Inflammation; N-Methyl-D-aspartic acid receptors; Nanoparticles; Neurobiology; Neurodegenerative diseases; Neurofibrillary tangles; Neurofibrillary Tangles - metabolism; Neurosciences; Phosphorylation; Review Paper; Senile plaques; Synapses; Tau protein; Vascular system
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-023-01408-7

Alzheimer’s disease (AD) is the primary cause of dementia and is characterized by the death of brain cells due to the accumulation of insoluble amyloid plaques, hyperphosphorylation of tau protein, and the formation of neurofibrillary tangles within the cells. AD is also associated with other pathologies such as neuroinflammation, dysfunction of synaptic connections and circuits, disorders in mitochondrial function and energy production, epigenetic changes, and abnormalities in the vascular system. Despite extensive research conducted over the last hundred years, little is established about what causes AD or how to effectively treat it. Given the severity of the disease and the increasing number of affected individuals, there is a critical need to discover effective medications for AD. The US Food and Drug Administration (FDA) has approved several new drug molecules for AD management since 2003, but these drugs only provide temporary relief of symptoms and do not address the underlying causes of the disease. Currently, available medications focus on correcting the neurotransmitter disruption observed in AD, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which temporarily alleviates the signs of dementia but does not prevent or reverse the course of AD. Research towards disease-modifying AD treatments is currently underway, including gene therapy, lipid nanoparticles, and dendrimer-based therapy. These innovative approaches aim to target the underlying pathological processes of AD rather than just managing the symptoms. This review discusses the novel aspects of pathogenesis involved in the causation of AD of AD and in recent developments in the therapeutic armamentarium for the treatment of AD such as gene therapy, lipid nanoparticles, and dendrimer-based therapy, and many more. Graphical Abstract