Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin, China.
The Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
J Alzheimers Dis. 2017;60(1):87-95. doi: 10.3233/JAD-170383.
Expression of neuronal thread protein (NTP), which is considered to be related to neuritic sprouting and neuronal death, may be elevated in brain tissue, cerebrospinal fluid, and even urine in patients with Alzheimer's disease (AD).
In this study, we analyzed the correlation between urine AD-associated NTP (AD7c-NTP) level, and amyloid-β (Aβ) deposition, and clinical symptoms in AD and mild cognitive impairment (MCI).
Twenty-two patients with mild to moderate AD and 8 subjects with MCI were recruited. Aβ deposition was measured with [11C]-labeled Pittsburgh compound B (PiB)-positron emission tomography (PET) in all participants. Urine AD7c-NTP levels were measured using enzyme-linked immunosorbent assay. Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI) were used to evaluate cognitive function and behavioral psychological symptoms, respectively.
Fourteen (63.6%) of AD patients and 2 (25.0%) of MCI subjects were Aβ positive on PiB-PET. There was a significant difference in urine AD7c-NTP level between Aβ positive (2.27±2.22 ng/ml) and negative (0.55±0.60 ng/ml) subjects (p = 0.018). Using 1.46 ng/ml as a cut-off value, 68.8% of Aβ positive subjects showed elevated urine AD7c-NTP level, and 92.9% of Aβ negative subjects showed normal urine AD7c-NTP level. There were no relationships between urine AD7c-NTP level and MMSE and total NPI scores. However, AD7c-NTP level positively correlated with agitation score on NPI.
Urine AD7c-NTP had high specificity and moderate sensitivity in predicting Aβ deposition among patients with cognitive impairment. Furthermore, urine AD7c-NTP level strongly correlated with the symptom of agitation.
神经元丝蛋白(NTP)的表达被认为与神经突发芽和神经元死亡有关,在阿尔茨海默病(AD)患者的脑组织、脑脊液,甚至尿液中可能升高。
本研究分析了 AD 及轻度认知障碍(MCI)患者尿液 AD 相关 NTP(AD7c-NTP)水平与淀粉样蛋白-β(Aβ)沉积及临床症状的相关性。
纳入 22 例轻中度 AD 患者和 8 例 MCI 患者。所有参与者均采用[11C]标记的匹兹堡化合物 B(PiB)-正电子发射断层扫描(PET)测量 Aβ沉积。采用酶联免疫吸附试验测量尿液 AD7c-NTP 水平。采用简易精神状态检查量表(MMSE)和神经精神问卷(NPI)分别评估认知功能和行为心理症状。
14 例(63.6%)AD 患者和 2 例(25.0%)MCI 患者的 PiB-PET 呈 Aβ阳性。Aβ阳性(2.27±2.22ng/ml)和阴性(0.55±0.60ng/ml)患者的尿液 AD7c-NTP 水平存在显著差异(p=0.018)。以 1.46ng/ml 为截断值,68.8%的 Aβ 阳性患者尿液 AD7c-NTP 水平升高,92.9%的 Aβ 阴性患者尿液 AD7c-NTP 水平正常。尿液 AD7c-NTP 水平与 MMSE 和 NPI 总分均无相关性。然而,AD7c-NTP 水平与 NPI 的激越评分呈正相关。
在认知障碍患者中,尿液 AD7c-NTP 对预测 Aβ沉积具有较高的特异性和中等的敏感性。此外,尿液 AD7c-NTP 水平与激越症状强烈相关。