Pathophysiology of Alzheimer's disease: advances in drug development and therapeutic innovations

Abstract

Alzheimer's disease causes cognitive decline, and drug discovery focuses on its pathophysiology. Current research is concentrating not only on amyloid β markers and tangles but also on synaptic defects, mitochondrial dysfunction, and inflammation as key therapeutic targets. Treatments for the amyloid pathway include monoclonal antibodies (e.g., aducanumab and lecanemab) to remove formed Aβ. Ongoing preliminary studies of small molecules and beta-secretase inhibitors are indeed targeting Aβ production to interrupt this toxic cascade. Small molecule strategies involve using small molecules and antisense oligonucleotides to reduce tau hyperphosphorylation and its levels. Future treatments for neurodegenerative diseases aim to modulate microglial activation and cytokine signaling using potential NLRP3 inhibitors, for example, to balance the immune response. Biological mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) are being discussed for neurodegenerative treatment and stem cell therapy. Nanotechnology has improved drug delivery across the blood-brain barrier, resulting in better targeting and reduced toxicity. Gene editing via CRISPR-Cas9 gene therapy targeting the genetic basis of Alzheimer's disease is on the horizon. Biomarkers are assisting in identifying and monitoring treatment response in Alzheimer's disease, while novel uses of FDA-approved drugs offer new treatment options, improve management strategies, and potentially enhance patient outcomes.