A systematic evaluation of cortical GABA levels in transgenic mouse models of amyloid

Abstract

AbstractBackgroundRodent models that overexpress mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes have been widely applied in Alzheimer’s disease (AD) research. These models classically present amyloid plaque deposition in cortical and hippocampal areas and neurotransmission changes. Although amyloid‐related glutamatergic abnormalities have been extensively described, little is known about its effects on the GABAergic system. Thus, we aimed to examine GABA levels in the cortex of two transgenic amyloid mouse models.MethodWe systematically reviewed the literature following the PRISMA 2020 guidelines. PubMed and Web of Science databases were searched for studies reporting GABA levels in the cortex of APPswe/PSEN1dE9 and Tg2576 mice. We opted to evaluate only animals with mature amyloid plaques in their cortices, according to each mouse model previous characterization.ResultThe search identified 3576 papers. Seven records met the inclusion criteria (Tg2576: n = 21, mean age ± standard deviation (SD) = 14.7 ± 3.7 months; controls: n = 21; APPswe/PSEN1dE9: n = 25, mean age ± SD = 8.5 ± 4.1 months; controls: n = 25). Five out of seven results reported non‐significant differences in the GABA levels in multiple cortical regions, such as the frontal, pre‐frontal, and rhinal cortices of the Tg2576 mouse model, but two studies described that GABA is significantly decreased. Furthermore, all studies with the APP/PSEN1 model consistently reported decreased cortical GABA levels. Figure 1 provides a summary of our findings.ConclusionOur results suggest that APP and PSEN1 mutations may contribute to the decrease in the levels of GABA in cortical regions of amyloid models. Future meta‐analyses and clinical studies are needed to ascertain the consistency of the reported results.