Over-expression of human mutated APP transgene in the mouse brain induces differential gene expression profiles depending on the age of exposure

Although AD pathological features have been intensively examined in numerous scientific studies employing invertebrate and vertebrate model organisms, the exact underlying mechanisms remain poorly understood. Extracellular accumulation of amyloid beta (Aβ) peptides represents a pathological hallmark of AD and it has been considered as the initiation point of AD by the popular amyloid hypothesis.

In the current study, we aim to address whether expression of a mutated APP transgene (APPSweInd) would provoke differential neurological outcomes depending on the age of exposure in mice. Towards this end, we employed a tetracycline-based inducible genetic system to target APPSweInd transgene expression to defined age intervals initiated at adulthood, i.e., between 6-18 months (= mid-aged group) and 12-24 months (= aged group).