Intraneuronal A¦Â immunoreactivity is not a predictor of brain amyloidosis-¦Â or neurofibrillary degeneration

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• 作者：Jerzy Wegiel ; Izabela Kuchna ; Krzysztof Nowicki ; Janusz Frackowiak ; Bozena Mazur-Kolecka ; Humi Imaki ; Jarek Wegiel ; Pankaj D. Mehta ; Wayne P. Silverman and Barry Reisberg ; et al.
• 关键词：Intraneuronal amyloid ; β ; ; Plaques ; Tangles ; Down syndrome ; Alzheimer’ ; s disease
• 刊名：Acta Neuropathologica
• 出版年：2007
• 出版时间：April, 2007
• 年：2007
• 卷：113
• 期：4
• 页码：389-402
• 全文大小：805 KB

文摘

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ_17–40/42). The presence of N-terminally truncated Aβ_17–40 and Aβ_17–42 in the control brains was confirmed by Western blotting and the identity of Aβ_17–40 was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ_17–42 immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism.