Cerebellar diffuse amyloid plaques are derived from dendritic Aβ42 accumulations in Purkinje cells

β-amyloid1–42 (Aβ42)-rich amyloid plaques (APs) may be derived from destroyed neurons that were burdened with extensive intracellular Aβ42 accumulations. Since most cells that accumulate Aβ42 express the α7 nicotinic acetylcholine receptor (α7nAChR), we examined the relationship between the intracellular accumulation of Aβ42 and the expression of the α7nAChR in cells from the cerebellum of sporadic Alzheimer’s disease (AD) patients. Aβ42, but not Aβ40 or Aβ43, accumulates intracellularly in Purkinje, Golgi II, stellate and basket cells in the AD cerebellum, all of which express the α7nAChR. Aβ42 deposits were also prominent within dendrites of Purkinje cells, especially at points of their bifurcation that were often occluded with this material. Diffuse APs appeared to represent the remnants of destroyed Aβ42-laden segments of Purkinje cell dendritic trees. Similarly, the accumulation of Aβ42 and early loss of Golgi II cells in AD cerebella correlated directly to their high level of α7nAChR expression. Furthermore, the presence and relative abundance of neuron-derived Aβ42/α7nAChR-positive materials within Bergman glia may be indicative of the stage of AD. These data are consistent with a role for the α7nAChR in mediating intracellular Aβ42 accumulation and also support the notion that the intracellular and intradendritic accumulation of Aβ42 may eventually result in cell lysis and the formation of APs.