CRISPR–Cas9 mediated repression of BACE1 for amyloid-beta reduction in early-stage Alzheimer’s disease: A meta-analysis

Objective: To assess the efficacy of CRISPR–Cas9-mediated repression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in reducing amyloid-beta (Aβ) accumulation, neuropathological changes, and cognitive deficits in preclinical Alzheimer’s disease (AD) models. Data Sources: A systematic search (2017–2024) was conducted in PubMed, Scopus, Web of Science, and Google Scholar, following PRISMA 2020 guidelines. Study Selection: Ten preclinical studies using rodent or neuronal AD models with CRISPR–Cas9 or CRISPR interference targeting BACE1 were included. Data Extraction: Extracted data included Aβ₄₀/₄₂ levels, BACE1 expression, plaque burden, neuronal integrity, neuroinflammation, and cognitive performance. Data Synthesis: Meta-analysis (RevMan 5.4, STATA 17) showed significant reductions in Aβ₄₀/₄₂ (SMD = –1.45), BACE1 expression (SMD = –1.73), and plaque burden (SMD = –1.38). Qualitative findings indicated improved neuronal survival, reduced inflammation, and cognitive benefits. Conclusions: CRISPR–Cas9 repression of BACE1 effectively attenuates amyloid pathology and supports cognitive improvements in preclinical AD models, underscoring its promise for translational CRISPR-based therapies. Keywords: Alzheimer’s Disease, CRISPR, BACE1, Amyloid-beta, Meta-analysis, Gene editing.