Distinct Aβ pathology in the olfactory bulb and olfactory deficits in a mouse model of Aβ and α‐syn co‐pathology.

Several degenerative brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous appearance of amyloid‐β (Aβ) and α‐synuclein (α‐syn) pathologies and symptoms that are similar, making it difficult to differentiate between these diseases. Until now, an accurate diagnosis can only be made by postmortem analysis. Furthermore, the role of α‐syn in Aβ aggregation and the arising characteristic olfactory impairments observed during the progression of these diseases is still not well understood. Therefore, we assessed Aβ load in olfactory bulbs of APP‐transgenic mice expressing APP695KM670/671NL and PSEN1L166P under the control of the neuron‐specific Thy‐1 promoter (referred to here as APPPS1) and APPPS1 mice co‐expressing SNCAA30P (referred to here as APPPS1 × [A30P]aSYN). Furthermore, the olfactory capacity of these mice was evaluated in the buried food and olfactory avoidance test. Our results demonstrate an age‐dependent increase in Aβ load in the olfactory bulb of APP‐transgenic mice that go along with exacerbated olfactory performance. Our study provides clear evidence that the presence of α‐syn significantly diminished the endogenous and seed‐induced Aβ deposits and significantly ameliorated olfactory dysfunction in APPPS1 × [A30P]aSYN mice. [ABSTRACT FROM AUTHOR]