Alzheimer’s disease (AD) poses a significant challenge in India, where the aging population is rapidly expanding, with over 5 million individuals currently affected and projections estimating a tripling by 2050. Traditional treatments have primarily targeted amyloid-beta (Aβ) plaques, with recent monoclonal antibodies like lecanemab and donanemab showing promise in slowing cognitive decline. However, these therapies fail to reverse brain damage or restore function, highlighting the limitations of single-target strategies. A groundbreaking review by Professor Yan-Jiang Wang and colleagues, published in *Science China Life Sciences*, argues that AD’s complexity demands a paradigm shift. Rather than isolating one cause, the disease emerges from interconnected factors including Aβ accumulation, Tau protein tangles, genetic predispositions, aging-related cellular changes, and systemic health issues. For Indian doctors managing diverse patient profiles—often complicated by comorbidities like diabetes and hypertension—this holistic perspective could transform clinical practice, emphasizing early intervention and personalized care to mitigate the socioeconomic burden on families and healthcare systems.
The review delves into key mechanisms reshaping AD research. Beyond Aβ, Tau hyperphosphorylation drives neurofibrillary tangles and neuronal loss, suggesting dual-target therapies for enhanced efficacy. Genetic factors, such as APOE ε4 variants prevalent in certain Indian populations, underscore the potential of CRISPR/Cas9 gene editing as a preventive tool. Aging, the primary risk factor, involves mitochondrial dysfunction, senescent cell accumulation, and DNA damage; emerging senolytic drugs could clear these cells to preserve brain health. Systemic influences, including insulin resistance, cardiovascular issues, and gut microbiome imbalances, link AD to whole-body health, opening avenues for repurposing diabetes medications or gut-brain axis interventions. The authors advocate integrated strategies, leveraging advanced models like human iPSC-derived organoids for drug testing and biomarkers such as plasma pTau217 for precision medicine. This multidisciplinary approach, combining neurology, genetics, and geriatrics, could make AD manageable or preventable. As Indian specialists navigate resource constraints, adopting these insights through collaborative research and public health initiatives may improve outcomes, reducing the disease’s devastating impact on cognition and quality of life.
