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 (A beta) 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 A beta 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 A beta 1-42 (monomers and oligomers, respectively) into the mouse OB and tracked the spreading of A beta to connected brain regions over 3 days. The results showed that both A beta 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 A beta 1-42 spread more efficiently and induced more neuronal apoptosis in the affected brain regions compared to monomeric A beta 1-42. Therefore, the study provides evidence that A beta peptides can transfer via neural connections and the pattern of A beta peptide spreading provides understanding to manage AD.