Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Abstract

Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/ PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.

Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe×PS1Δe9 transgenic mouse model of Alzheimer's disease

“…These results suggest that different forms of tau and amyloid pathology may alter TSPO expression differently in vivo (Jansen et al 2013). This may be because of potential differences in type of amyloid, aggregation properties, expression levels and age of pathology emergence between different models of AD, which may differently affect the glial response (Stalder et al 1999;Xiong et al 2011;Huang et al 2016). In contrast, TSPO expression was only visible in the vessels in WT animals which are in agreement with previous report demonstrating the expression of TSPO in vessels (Turkheimer et al 2007).…”

“…; Huang et al . ). In contrast, TSPO expression was only visible in the vessels in WT animals which are in agreement with previous report demonstrating the expression of TSPO in vessels (Turkheimer et al .…”

“…) suggesting that APP mutations are not sufficient to cause neuronal loss that is observed in human AD and models with tau abnormalities but in contrast with Huang et al . () who reported a decrease (~20%) in NeuN staining and hippocampal atrophy (~20–30%). On the other hand, amyloid pathology induced cognitive decline and resulted in accelerated NAA loss with age in TG compared to WT mice.…”

Age‑dependent concomitant changes in synaptic function and GABAergic pathway in the APP/PS1 mouse model

“…These models have been shown to mimic various of the AD related clinical pathology such as amyloid beta (Aβ) plaque load accumulation, deficits in synaptic function and structure, as well as deficits in learning and memory (Jankowsky et al 2001, Trinchese et al 2004, Radde et al 2006, Huang et al 2016.…”

“…Transgenic mice of the APP/PS1 models overexpress Swedish family mutated forms of the human amyloid precursor protein (APPswe) and various mutation in Presenilin1 result in age-dependent and region-specific amyloid deposition (Jankowsky et al 2001, Fitzjohn et al 2010, Huang et al 2016. APP/PS1 mice spontaneously show seizures, which are believed to be associated to an imbalance in the excitatory/inhibitory function (i.e.…”