Synergistic effects of hIAPP and Aβ_1-42 impaired the olfactory function associated with the decline of adult neurogenesis in SVZ

According to many in the field，the prevalence of Alzheimer's disease (AD) in type II diabetes (T2DM) populations is considerably higher than that in the normal population. Human islet amyloid polypeptide (hIAPP) is considered to be a common risk factor for T2DM and AD. Preliminary observations around T2DM animal model show that the decrease of adult neural stem cells (NSCs) in the subventricular zone (SVZ) is accompanied by olfactory dysfunction. Furthermore, impaired olfactory function could serve as to an early predictor of neurodegeneration，which is associated with cognitive impairment. However, the synergistic effects between hIAPP and amyloid-beta (Aβ) _1-42 in the brain and the neurodegeneration remains to be further clarified. In this study, olfactory capacity, synaptic density, status of NSC in SVZ, and status of newborn neurons in olfactory bulb (OB) were assessed 6 months after stereotactic injection of oligomer Aβ_1-42 into the dens gyrus (DG) of hIAPP-/+ mice or wild-type homogenous mice. Our results set out that Aβ₄₂ and amylin co-localized into OB and raised Aβ₄₂ deposition in hIAPP^-/+ mice compared with wild-type brood mice. In addition, 6 months after injection of Aβ_1-42 in hIAPP^-/+ mice, these mice showed increased olfactory dysfunction, significant loss of synapses, depletion of NSC in SVZ, and impaired cell renewal in OB. Our present study suggested that the synergistic effects between hIAPP and Aβ_1-42 impairs olfactory function and was associated with decreased neurogenesis in adults with SVZ.