Toward Reproducibility in Preclinical Alzheimer’s Research: The Case for Standardizing Aβ₁–₄₂-Induced Rodent Models

Introduction: Animal-induced models are necessary to bridge the translational gap between transgenic models and clinical trials. Although several models are standard, experimental designs differ, and protocols are not standardized.

Methods: A PRISMA-guided search was performed in PubMed, Embase, and Cochrane, and 60 studies with Aβ1-42 injected into rats were included. Primary outcomes were rat strain, sex, injection site, and dose. Secondary outcomes followed the time between induction and cognitive testing. Data was analyzed using JASP statistics program and applying descriptive statistics, t-tests, chi-square, and correlations.

Results: Bilateral injections showed up in 65% of the studies, most often in Wistar rats (64%), and hit either the intracerebroventricular (i.c.v., 48.7%) or intrahippocampal (i.h.c., 51.3%) regions. Most unilateral models—85.7%—used i.c.v. injections. On average, researchers injected 3.8 ± 2.1 µl in bilateral setups and 4.9 ± 2.6 µl in unilateral ones. They ran behavior tests about 18.4 ± 10.6 days after bilateral and 20.7 ± 12.9 days after unilateral injections. Statistically, those differences were not significant (p > 0.05).

Conclusions: The field still lacks a standard way to run Aβ₁–₄₂-based Alzheimer’s models. Even when timing and doses line up, choices around animal strain, injection site, and laterality vary widely. Establishing standardized reference parameters—dose, site, and timing—appears critical to enhance reproducibility and strengthen the translational validity of preclinical Alzheimer’s research.