Establishing a Type 2 Diabetes phenotype in APPxhQC transgenic mice expressing N‐terminally modified pGlu Aβ peptides.

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of amyloid beta (Aβ) plaques in the brain. Aβ peptides are commonly subjected to post‐translational modifications like truncation known to play pivotal role in Aβ plaque aggregation. N‐terminally truncated Aβ peptides containing pyroglutamatic acid (pGlu) catalyzed by glutaminyl cyclase (QC) e.g., pGlu3‐Aβ (3‐40/42) are the major Aβ peptide fragments within the core of the neuritic plaques and correlate with disease severity and progression. Type 2 diabetes (T2D) is one of the major risk factors associated with AD and compelling evidence supports the notion that insulin resistance, a key feature of T2D, is involved in AD‐type neurodegeneration. Hence, in this study, we aim to establish a T2D phenotype in APPxhQC transgenic using low‐dose Streptozocin injection in combination with high fat diet (HFD).