Elucidating the molecular targets in Alzheimer's disease: Advances and therapeutic implications

Alzheimer's disease (AD), the most prevalent form of dementia, is intrinsically linked to the biological processes of ageing, which serve as its greatest risk factor. As global life expectancy rises, age-associated neurodegenerative disorders like AD impose an escalating burden on public health systems and economies. Ageing is accompanied by a complex interplay of cellular and molecular alterations, including oxidative stress, mitochondrial dysfunction, impaired proteostasis, chronic neuroinflammation, and epigenetic drift, all of which converge to disrupt neuronal integrity and function. In AD, these ageing-related mechanisms accelerate pathological hallmarks such as amyloid-β plaque deposition, tau hyperphosphorylation, synaptic loss, and neurodegeneration. Recent advances in molecular neuroscience have unveiled a spectrum of novel targets involved in the pathogenesis of AD, ranging from secretases and tau kinases to microglial receptors and mitochondrial bioenergetic regulators. This review elucidates the therapeutic strategies aimed at modulating these targets, including the use of small-molecule inhibitors, monoclonal antibodies, gene therapies, and epigenetic modifiers. Additionally, the impact of blood-brain barrier integrity on neuronal energy metabolism and its correlation with AD pathology is examined. The findings underscore the importance of interdisciplinary approaches in AD research, highlighting future directions and challenges in developing effective treatments. By advancing our understanding of the molecular nexus of AD, this work aims to contribute to the ongoing efforts to mitigate the effects of this debilitating condition and improve patient outcomes.