BETA-AMYLOID PEPTIDE AND AMYLOID PRECURSOR PROTEINS IN OLFACTORY MUCOSA OF PATIENTS WITH ALZHEIMERS-DISEASE, PARKINSONS-DISEASE, AND DOWN-SYNDROME
BETA-AMYLOID PEPTIDE AND AMYLOID PRECURSOR PROTEINS IN OLFACTORY MUCOSA OF PATIENTS WITH ALZHEIMERS-DISEASE, PARKINSONS-DISEASE, AND DOWN-SYNDROME
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DOI：
10.1177/000348949510400812
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发表时间：
1995-08-01
影响因子：
1.4
通讯作者：
TROJANOWSKI, JQ
中科院分区：
文献类型：
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作者：
CRINO, PB;MARTIN, JA;TROJANOWSKI, JQ
营养不良的神经突起存在于阿尔茨海默病(AD)、帕金森病(PD)和唐氏综合征(DS)患者的嗅觉上皮(OE)中，偶尔也存在于正常人中。来自AD患者的培养的嗅神经母细胞产生含有β-淀粉样蛋白(Aβ)的羧基末端淀粉样前体蛋白(APP)片段，但尚不清楚患有或不患有AD、PD或DS的人的OE中是否存在Aβ和/或APP片段的沉积。为了确定Aβ是否在OE中原位积聚，我们使用抗Aβ的多克隆和单克隆抗体以及APP中的侧翼序列，对AD、PD和AD患者(PD/AD)、DS和AD(DS/AD)以及正常对照的死后嗅黏膜样本进行了探测。用硫代黄素-S法和电子显微镜对OE标本进行了观察。12例AD患者中有10例，3例PD/AD患者中有2例，4例DS/AD患者中有3例，10例成人对照中有3例，6例胎儿中有4例有Aβ标记。Aβ染色见于OE的基底1/3、穿过固有层的轴突和OE内的化生呼吸道上皮。抗其他APP结构域的抗体染色了患者和对照组的OE。在9例AD患者和少数PD/AD和DS/AD患者中，有8例患者OE基底部1/3处可见硫代黄素-S染色，而在3例对照组中仅见稀有细胞表达。电子显微镜未显示OE中的淀粉样纤维。这些数据表明，Aβ的沉积发生在各种情况下，并不局限于AD、PD或DS患者。
Dystrophic neurites are present in olfactory epithelium (OE) of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and Down syndrome (DS) and occasionally in normal individuals. Cultured olfactory neuroblasts from AD patients generate carboxy terminal amyloid precursor protein (APP) fragments that contain beta-amyloid (A beta), but it is not known if deposits of A beta and/or APP fragments occur in the OE of individuals with or without AD, PD, or DS. To determine if A beta accumulates in the OE in situ, we probed postmortem samples of olfactory mucosa from patients with AD, PD and AD (PD/AD), and DS and AD (DS/AD), as well as from controls, using polyclonal and monoclonal antibodies to A beta and flanking sequences in APPs. Samples of OE also were examined by thioflavin-S and electron microscopy. Labeling of A beta was observed in 10 of 12 AD cases, 2 of 3 PD/AD cases; 3 of 4 DS/AD cases, 3 of 10 adult controls, and 4 of 6 fetal cases. The A beta staining was seen in the basal third of the OE, in axons projecting through the lamina propria, and in metaplastic respiratory epithelium within the OE. Antibodies to other APP domains stained the OE of patients and controls. Thioflavin-S staining was present in the basal third of the OE of 8 of 9 AD patients and several PD/AD and DS/AD patients, but only in rare cells of 3 controls. Electron microscopy did not reveal amyloid fibrils in the OE. These data suggest that deposition of A beta occurs in a variety of circumstances and is not restricted to patients with AD, PD, or DS.