Stem Cell Therapy in Alzheimer’s Disease: a Scoping Review of Safety, Efficacy and Clinical Insights

Abstract

Alzheimers disease (AD) remains a progressive neurodegenerative disorder with limited disease-modifying treatment approaches. This scoping review aimed to systematically examine and critically evaluate the existing clinical evidence on stem cell therapy for AD, focusing on therapeutic efficacy, safety, cognitive and functional outcomes, neuroimaging, and improvement of biological markers for disease progression. A search of PubMed, Google Scholar, and ClinicalTrials.gov identified 3158 records, of which seven clinical studies met the eligibility criteria. The included studies comprised early-phase clinical trials, pilot studies, and observational studies involving predominantly patients with mild to moderate AD. Mesenchymal, umbilical cord-derived, and telomerase-positive stem cell therapies administered through intravenous, intracerebroventricular, intranasal, and intrathecal routes demonstrated encouraging preliminary signals across cognitive, functional, neuroimaging, and biomarker outcomes. Improvements or stabilization in Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer’s disease assessment scale cognitive subscale (ADAS-Cog), and functional measures were reported, alongside reductions in CSF amyloid-β or tau-related biomarkers and evidence of reduced hippocampal atrophy in selected studies. Across the included studies, stem cell therapies showed generally favorable tolerability, with predominantly transient and mild adverse events. Current clinical evidence supports the potential of stem cell therapy as a biologically active and potentially disease-modifying approach for AD. However, definitive conclusions remain limited by small sample sizes, heterogeneous cell products and delivery protocols, methodological variability, and limited long-term follow-up. Future multicenter, Phase IIb/III trials with standardized cell products, administration protocols, outcome measures, and long-term safety monitoring are required to establish clinical efficacy and translational feasibility.