Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in Alzheimer's disease

What is it about?

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder, causing a progressive decline of intellectual faculties, impairment of behavior and social performance, and impairment of speech eloquence, associated with various neurological manifestations based on a variable neuropathological background. Edinger-Westphal nucleus is a selective target of Alzheimer pathology early in the course of the disease. We attempted to determine the morphological alterations of the dendrites and the dendritic spines in Edinger-Westphal nucleus of 7 cases that fulfilled the diagnostic criteria for Alzheimer’s disease. For the histological study, we applied (a) routine neuropathological techniques and (b) rapid Golgi method. We proceeded to 3D neuronal reconstruction for the estimation of dendritic and spinal changes in Alzheimer’s disease. The morphological and morphometric analysis revealed a substantial neuronal loss and synaptic alterations in Edinger-Westphal nucleus in all the cases of Alzheimer’s disease. Distal dendritic branches are prominently affected. The neuronal loss and alteration of the spines in Edinger-Westphal nucleus in Alzheimer’s disease may be related to the exaggerated pupillary reaction to cholinergic antagonists. Furthermore, the vulnerability of distal branches to Alzheimer’s disease might be related to neuroplasticity impairment.

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Why is it important?

Gallyas technique revealed neurofibrillary degeneration in the majority of the EW neurons. Two types of plaque-like deposits were mainly encountered in AD EW nuclei. Typical and compact amyloid cored plaques, were mainly observed, while diffuse plaques were seen outside the EW nuclei.An intriguing result of the present study is the prominent degeneration of the more distal branches of EW nucleus’ neurons. From previous assays on similar topics, it is now acknowledged that distal branches are linked in the majority with neuronal plasticity and vice versa, therefore playing an important role in the process of learning and neuronal adaptation. On the other hand, neuronal plasticity is grossly affected by the accumulation of NFTs and is related to cholesterol metabolism, and therefore, at least ultimately, APP metabolism

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