Mufson E J, Ma S Y, Cochran E J, Bennett D A, Beckett L A, Jaffar S, Saragovi H U, Kordower J H
Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
J Comp Neurol. 2000 Nov 6;427(1):19-30. doi: 10.1002/1096-9861(20001106)427:1<19::aid-cne2>3.0.co;2-a.
Recent studies indicate that there is a marked reduction in trkA-containing nucleus basalis neurons in end-stage Alzheimer's disease (AD). We used unbiased stereological counting procedures to determine whether these changes extend to individuals with mild cognitive impairment (MCI) without dementia from a cohort of people enrolled in the Religious Orders Study. Thirty people (average age 84.7 years) came to autopsy. All individuals were cognitively tested within 12 months of death (average MMSE 24.2). Clinically, 9 had no cognitive impairment (NCI), 12 were categorized with MCI, and 9 had probable AD The average number of trkA-immunoreactive neurons in persons with NCI was 196, 632 +/- 12,093 (n = 9), for those with MCI it was 106,110 +/- 14,565, and for those with AD it was 86,978 +/- 12,141. Multiple comparisons showed that both those with MCI and those with AD had significant loss in the number of trkA-containing neurons compared to those with NCI (46% decrease for MCI, 56% for AD). An analysis of variance revealed that the total number of neurons containing trkA immunoreactivity was related to diagnostic classification (P < 0.001), with a significant reduction in AD and MCI compared to NCI but without a significant difference between MCI and AD. Cell density was similarly related to diagnostic classification (P < 0.001). There was a significant correlation with the Boston Naming Test and with a global score measure of cognitive function. The number of trkA-immunoreactive neurons was not correlated with MMSE, age at death, education, apolipoprotein E allele status, gender, or Braak score. These data indicate that alterations in the number of nucleus basalis neurons containing trkA immunoreactivity occurs early and are not accelerated from the transition from MCI to mild AD.
近期研究表明，在晚期阿尔茨海默病（AD）中，含trkA的基底核神经元显著减少。我们采用无偏倚的立体学计数程序，以确定这些变化是否延伸至参加宗教团体研究的一组无痴呆的轻度认知障碍（MCI）个体。30人（平均年龄84.7岁）接受了尸检。所有个体在死亡前12个月内均接受了认知测试（平均简易精神状态检查表评分为24.2）。临床上，9人无认知障碍（NCI），12人被归类为MCI，9人患有可能的AD。NCI患者中trkA免疫反应性神经元的平均数量为196,632±12,093（n = 9），MCI患者为106,110±14,565，AD患者为86,978±12,141。多重比较显示，与NCI患者相比，MCI患者和AD患者含trkA神经元的数量均显著减少（MCI减少46%，AD减少56%）。方差分析显示，含trkA免疫反应性的神经元总数与诊断分类相关（P < 0.001），与NCI相比，AD和MCI均显著减少，但MCI和AD之间无显著差异。细胞密度同样与诊断分类相关（P < 0.001）。与波士顿命名测试和认知功能的总体评分测量存在显著相关性。trkA免疫反应性神经元的数量与简易精神状态检查表评分、死亡年龄、教育程度、载脂蛋白E等位基因状态、性别或Braak评分均无相关性。这些数据表明，含trkA免疫反应性的基底核神经元数量的改变在早期就已出现，且从MCI过渡到轻度AD时并未加速。
