Injected Amyloid Beta in the Olfactory Bulb Transfers to Other Brain Regions via Neural Connections in Mice.

Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and pathological accumulation of amyloid plaques in the brain. It has been proposed that the prion-like spreading of amyloid beta (Aβ) protein could contribute to the progression of the disease. Olfactory bulb (OB) is one of the earliest brain regions affected in AD and olfaction is easily impaired prior to cognitive symptoms. However, it remains unclear whether Aβ accumulation in the OB would spread along olfactory projections to other connected brain regions and trigger further neurodegeneration. In the present study, we experimentally injected recombinant human Aβ1-42 (monomers and oligomers, respectively) into the mouse OB and tracked the spreading of Aβ to connected brain regions over 3 days. The results showed that both Aβ monomers and oligomers were rapidly and readily transferred from the injection site to interconnected brain regions in a neural connection manner and triggered neuronal apoptosis in the affected brain regions. Oligomeric Aβ1-42 spread more efficiently and induced more neuronal apoptosis in the affected brain regions compared to monomeric Aβ1-42. Therefore, the study provides evidence that Aβ peptides can transfer via neural connections and the pattern of Aβ peptide spreading provides understanding to manage AD.