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

P-amyloid(1-42) (Abeta42)-rich amyloid plaques (APs) may be derived from destroyed neurons that were burdened with extensive intracellular Abeta42 accumulations. Since most cells that accumulate Abeta42 express the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), we examined the relationship between the intracellular accumulation of Abeta42 and the expression of the alpha7nAChR in cells from the cerebellum of sporadic Alzheimer's disease (AD) patients. Abeta42, but not Abeta40 or Abeta43, accumulates intracellularly in Purkinje, Golgi II, stellate and basket cells in the AD cerebellum, all of which express the alpha7nAChR. Abeta42 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 Abeta42-laden segments of Purkinje cell dendritic trees. Similarly, the accumulation of Abeta42 and early loss of Golgi II cells in AD cerebella correlated directly to their high level of alpha7nAChR expression. Furthermore, the presence and relative abundance of neuron-derived Abeta42/alpha7nAChR-positive materials within Bergman glia may be indicative of the stage of AD. These data are consistent with a role for the alpha7nAChR in mediating intracellular Abeta42 accumulation and also support the notion that the intracellular and intradendritic accumulation of Abeta42 may eventually result in cell lysis and the formation of APs. (C) 2002 Elsevier Science Inc. All rights reserved.