Exploring fish protein hydrolysates: A promising frontier in Alzheimer's disease treatment modalities - A systematic review and meta-analysis

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying treatments. Bioactive peptides from fish protein hydrolysates (FPHs) have been proposed as multifunctional neuroprotective agents. This systematic review and meta-analysis synthesized evidence from 70 preclinical studies to evaluate four AD-relevant bioactivities-antioxidant (AO), angiotensin-converting enzyme inhibition (ACEi), acetylcholinesterase inhibition (AChEi), and amyloid-beta aggregation inhibition (ABi). FPHs demonstrated significant pooled benefits across all outcomes (p less than 0.001), although heterogeneity was high and effect magnitudes varied by domain. Subgroup analyses showed larger effects in vitro than in vivo, reflecting a predominance of early-stage mechanistic research. Evidence for AChEi and especially ABi remains limited, with very few in vivo studies, underscoring a major translational gap. Funnel plot asymmetry and Egger regression indicated possible publication bias, suggesting that reported effect sizes may be inflated. Collectively, FPHs show consistent multi-target neuroprotective potential, but future work must address methodological variability, expand in vivo validation, and undertake pharmacokinetic and clinical investigations to determine whether these peptides can advance toward therapeutic application in AD.