Potential of Nerve Growth Factor (NGF)- and Brain-Derived Neurotrophic Factor (BDNF)-Targeted Gene Therapy for Alzheimer’s Disease: A Narrative Review

Abstract

Alzheimer's disease (AD) involves progressive degeneration of cholinergic and synaptic networks, leading to cognitive decline. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), essential for neuronal survival and plasticity, have gained therapeutic interest. Particularly through gene therapy approaches. Preclinical studies have shown improved neuronal integrity and memory restoration. Nonetheless, clinical translation faces significant challenges, including invasive delivery, vector limitations, and receptor dysregulation. Gene therapy must be focused on precision-targeted, minimally invasive delivery systems, controlled gene expression, and early-stage intervention. This review critically evaluates NGF- and BDNF-based gene therapies, highlighting advances, limitations, and future directions that may position neurotrophin modulation as a viable disease-modifying strategy in AD.