Distinct A beta pathology in the olfactory bulb and olfactory deficits in a mouse model of A beta and alpha-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-beta (A beta) and alpha-synuclein (alpha-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 alpha-syn in A beta aggregation and the arising characteristic olfactory impairments observed during the progression of these diseases is still not well understood. Therefore, we assessed A beta load in olfactory bulbs of APP-transgenic mice expressing APP695(KM670/671NL) and PSEN1(L166P) under the control of the neuron-specific Thy-1 promoter (referred to here as APPPS1) and APPPS1 mice co-expressing SNCA(A30P) (referred to here as APPPS1 x [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 A beta 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 alpha-syn significantly diminished the endogenous and seed-induced A beta deposits and significantly ameliorated olfactory dysfunction in APPPS1 x [A30P]aSYN mice.