Abstract
We recently reported that Alzheimer's disease (AD) with amygdala Lewy bodies (ALB) is a distinct form of alpha-synucleinopathy that occurs in advanced AD. In AD/ALB the alpha-synuclein pathology correlated with tau pathology, but not amyloid plaques, and there was often co-localization of tau and alpha-synuclein in the same neuron. Given the anatomical connectivity of the anterior olfactory nucleus and the amygdala, which receives axonal projections from the olfactory bulb, we hypothesized that there might be a relationship between tau and alpha-synuclein pathology in the olfactory bulb and the amygdala in AD. We screened for alpha-synuclein pathology in the olfactory bulb in AD with and without ALB, and investigated its relationship with tau pathology. In 38 of 41 (93%) AD/ALB cases and 4 of 21 (19%) AD cases without ALB (AD/non-ALB), alpha-synuclein pathology was detected in the olfactory bulb. Double immunolabeling at the light and electron microscopic levels revealed co-localization of tau and alpha-synuclein in the olfactory bulb neurons and neurites. The severity of tau pathology correlated with alpha-synuclein pathology in the olfactory bulb. In addition, alpha-synuclein pathology in the olfactory bulb correlated with alpha-synuclein pathology in amygdala. Tau pathology was greater in both the olfactory bulb and amygdala in AD/ALB than in AD/non-ALB, but there was no difference in tau pathology between the two groups in other brain regions assessed. The present study shows that in AD/ALB, the olfactory bulb is nearly equally vulnerable to tau and alpha-synuclein pathology as the amygdala and suggests that neurodegeneration in these two anatomical regions is linked.