Role of Ageing in Alzheimer's Therapeutics

   Background. The biggest risk factor for Alzheimer’s disease (AD) is aging, contributing to impaired clearance of tau and amyloid-beta (Aβ) proteins, microglial senescence, endoplasmic reticulum (ER) stress, lipid dysregulation, and excitotoxicity. Objective. This review investigates how aging speeds up the pathophysiology of AD and evaluates emerging geroscience-based interventions targeting biological aging mechanisms to delay or prevent cognitive decline.

   Material and methods. A narrative review of the literature from 2015 to 2025 was conducted, integrating longitudinal studies, meta-analyses, and preclinical models that examine the aging — AD interface. The MEDLINE, Embase, Cochrane, Google Scholar, and PubMed databases were searched using specifi cally related keywords, such as ageing, AD, AD pathology, anti-aging strategies, and AD therapies.

   Results. From the initial search, more than 150 studies were excluded, and only 100 studies were selected for this review. After revision also duplicated 30 studies were removed. Ultimately, the review comprised seventy studies. Most of these studies discussed aging-related mechanisms — glymphatic dysfunction, APOE ε4-associated lipid transport impairment, BDNF depletion, and glutamate excitotoxicity, and anti-ageing strategies such as lifestyle interventions (e.g., physical activity, sleep optimization, cognitive engagement) and medical and biological therapies for AD.

   Conclusion. Targeting aging mechanisms offers a paradigm shift in AD prevention and treatment; however, multidisciplinary collaboration is essential to translate geroscience into clinical practice. The integration of lifestyle and pharmacological strategies may yield synergistic neuroprotective benefi ts. Future research should focus on integrated, multimodal interventions that combine lifestyle modification with pharmacological and biological therapies. Tailored approaches — based on genetic risk profi les (e.g., APOE status), comorbidities, and individual aging trajectories — may optimize clinical outcomes. To evaluate the long-term safety and effectiveness of innovative treatments like senolytics, epigenetic modulators, and stem cell-based therapies in older populations, extensive, longitudinal clinical trials are also required. Developments in biological age biomarkers, machine learning, and systems biology have the potential to improve risk assessment and therapy customization.

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