de la Monte S M, Volicer L, Hauser S L, Wands J R
Department of Neuropathology, Massachusetts General Hospital, Harvard Medical School, Boston.
Ann Neurol. 1992 Dec;32(6):733-42. doi: 10.1002/ana.410320606.
Neuronal thread protein is a recently characterized, approximately 20-kd protein that accumulates in brains with Alzheimer's disease (AD) lesions. This study examined whether concentrations of neuronal thread protein (NTP) were also increased in the cerebrospinal fluid (CSF) of individuals with probable (clinically diagnosed) and definite (histopathologically proved) AD. Using a highly sensitive three-site monoclonal antibody-based immunoradiometric assay, we measured NTP concentrations in CSF from 84 patients with probable AD and mild dementia (duration, 4.05 +/- 0.36 years), 45 with Parkinson's disease and minimal or no dementia (duration, 4.73 +/- 0.78 years), 73 with multiple sclerosis, and 73 nondemented control subjects. NTP concentrations were also measured in postmortem ventricular fluid and temporal lobe neocortex extracts from 31 subjects with histopathologically proved AD and 14 age-matched control subjects. The mean concentration of NTP in the CSF was higher in AD (4.15 +/- 0.25 ng/ml; 95% confidence interval [CI] limits, 3.65-4.65) than in Parkinson's disease (1.96 +/- 0.16 ng/ml; 95% CI, 1.65-2.27), multiple sclerosis (1.6 +/- 0.14 ng/ml; 95% CI limits, 1.33-1.88), or control subjects (1.27 +/- 0.06 ng/ml; 95% CI limits, 1.15-1.40) (p < 0.001). In addition, 70% of the patients with probable AD had concentrations of NTP in CSF that were higher than 2.5 ng/ml (> upper 99% CI limit in the control group), compared with 23% of Parkinson's disease patients, 11% of multiple sclerosis patients, and 4% of control subjects. The mean concentrations of NTP in the ventricular fluid and brain tissue from individuals with documented AD and end-stage dementia were threefold higher than the levels detected in the CSF from the remaining patients with probable AD and mild dementia. Moreover, of 9 patients with AD, postmortem brain and CSF manifested 5- to 50-fold higher levels of NTP compared with the CSF samples obtained an average of 6 years earlier. These findings demonstrate that NTP levels are elevated in the CSF of individuals with AD and that NTP levels in the CSF increase strikingly with progression of dementia and neuronal degeneration.
神经元纤维蛋白是一种最近被鉴定出来的、分子量约为20kd的蛋白质，它在患有阿尔茨海默病（AD）病变的大脑中蓄积。本研究检测了可能（临床诊断）和确诊（组织病理学证实）AD患者脑脊液（CSF）中神经元纤维蛋白（NTP）的浓度是否也升高。我们使用一种基于高灵敏度三位点单克隆抗体的免疫放射分析方法，测定了84例可能患有AD且轻度痴呆（病程4.05±0.36年）、45例患有帕金森病且轻度或无痴呆（病程4.73±0.78年）、73例患有多发性硬化症以及73例无痴呆对照者的CSF中NTP的浓度。我们还测定了31例经组织病理学证实患有AD的受试者和14例年龄匹配对照者死后脑室液和颞叶新皮质提取物中的NTP浓度。AD患者CSF中NTP的平均浓度（4.15±0.25 ng/ml；95%可信区间[CI]范围，3.65 - 4.65）高于帕金森病患者（1.96±0.16 ng/ml；95%CI，1.65 - 2.27）、多发性硬化症患者（1.6±0.14 ng/ml；95%CI范围，1.33 - 1.88）或对照者（1.27±0.06 ng/ml；95%CI范围，1.15 - 1.40）（p < 0.001）。此外，70%的可能患有AD的患者CSF中NTP浓度高于2.5 ng/ml（>对照组99%CI上限），相比之下，帕金森病患者为23%，多发性硬化症患者为11%，对照者为4%。有记录的AD和终末期痴呆患者脑室液和脑组织中NTP的平均浓度比其余可能患有AD且轻度痴呆患者CSF中检测到的水平高3倍。此外，9例AD患者中，死后大脑和CSF中NTP水平比平均6年前采集的CSF样本高5至50倍。这些发现表明，AD患者CSF中NTP水平升高，且CSF中NTP水平随着痴呆和神经元变性的进展而显著增加。
