The objective of the experiment was to observe the quantifiable differences between SST, PV, CCK, and VIP interneurons in APP-Ki mice.

Recent studies in the APP-KI mice show that CA1 GABAergic cell types contribute to 30% of plaque load, especially the perisomatic INs in stratum pyramidale – same loci for plaque prevalence in human AD patients. Furthermore, specific GABAergic INs are shown to be particularly affected or lost in AD, such as the somatostatin (SST) and Calretinin INs. In this study, we are focusing on the SST, PV, CCK and VIP INs to quantify which neuron types are vulnerable versus which are resilient.

We crossed the APP-KI mice with VIP-Cre driver mice and performed stereotaxic injection in hippocampal area CA1of the resulting APP KI (+/+)/VIP Cre (+/-) and APP KI (-/-) /VIP Cre (+/-) progeny mice with a Cre dependent AAV virus to express the fluorophore TdTomato in CA1 VIP INs. The tissues were examined with a confocal microscope and analyzed with Fiji software.

We found that in older (9–12-month-old) APP-KI (+/+) mice, the number of tdTom+ VIP INs was decreased compared to their APP-KI (-/-) control counterparts.

Our study demonstrates a significant reduction in VIP interneurons (VIP INs) in the CA1 region of 9–12-month-old APP-KI (+/+) mice compared to controls. This highlights the selective vulnerability of VIP INs in Alzheimer’s disease (AD) pathology, providing insights into interneuron-specific contributions to AD progression and potential targets for therapeutic strategies.