背景:有初步证据表明生物标志物神经颗粒蛋白(Ng)可以将阿尔茨海默病(AD)与其他神经退行性疾病区分开来。因此,我们评估了(a)脑脊液(CSF)Ng水平区分AD和额颞叶变性(FTLD)病理以及同一疾病不同阶段的判别能力,(b)AD和FTLD病理学中Ng水平与认知表现之间的关系,和(c)AD连续体中CSFNg水平是否因载脂蛋白E(APOE)多态性而变化。
方法:主观认知能力下降(SCD)的参与者(n=33),由于AD引起的遗忘型轻度认知障碍(aMCI)(n=109),AD痴呆(n=67),MCI由于FTLD(n=25),和FTLD痴呆(n=29)从捷克脑老化研究中招募。单向协方差分析(ANCOVA)评估了诊断亚组中的Ng水平。线性回归评估了CSFNg水平之间的关系,记忆分数,和APOE多态性。
结果:与MCI-FTLD相比,aMCI-AD患者的Ng水平更高(F[1,134]=15.16,p<.001),与FTLD痴呆相比,AD痴呆(F[1,96]=4.60,p=0.029)。此外,与MCI-FTLD相比,FTLD-痴呆患者的Ng水平更高(F[1,54]=4.35,p=.034),与aMCI-AD(F[1,142]=10.72,p=.001)和AD-痴呆(F[1,100]=20.90,p<.001)相比,SCD参与者较低,SCD参与者与MCI-FTLD(F[1,58]=1.02,p=.491)或FTLD-痴呆(F[1,62]=2.27,p=.051)之间无差异。诊断亚组对Aβ1-42/Ng比值的主要影响也是显著的(F[4,263]=,p<.001)。我们发现Ng水平与总体记忆评分(β=-0.25,p=.154)或AD诊断亚组之间无显著关联,总体ADAPOEε4携带者和非携带者之间的这种关联差异不显著(β=-0.32,p=.358)。
结论:在迄今为止的第一项研究中,一项研究旨在评估由AD或FTLD引起的MCI和痴呆,CSFNg升高似乎是AD相关损害的早期生物标志物,但是它作为生物标志物的作用在痴呆症诊断后似乎减弱了,由此AD和FTLD中与痴呆相关的潜在过程可能开始合并。Aβ1-42/Ng比值比单独Ng更好地将AD与FTLD患者区分开来。CSFNg水平与AD或FTLD的记忆无关,表明Ng可能是疾病状态而不是认知缺陷的生物学标志。
BACKGROUND: There is initial evidence suggesting that biomarker neurogranin (Ng) may distinguish Alzheimer\'s disease (AD) from other neurodegenerative diseases. Therefore, we assessed (a) the discriminant ability of cerebrospinal fluid (CSF) Ng levels to distinguish between AD and frontotemporal lobar degeneration (FTLD) pathology and between different stages within the same disease, (b) the relationship between Ng levels and cognitive performance in both AD and FTLD pathology, and (c) whether CSF Ng levels vary by apolipoprotein E (APOE) polymorphism in the AD continuum.
METHODS: Participants with subjective cognitive decline (SCD) (n = 33), amnestic mild cognitive impairment (aMCI) due to AD (n = 109), AD dementia (n = 67), MCI due to FTLD (n = 25), and FTLD dementia (n = 29) were recruited from the Czech Brain Aging Study. One-way analysis of covariance (ANCOVA) assessed Ng levels in diagnostic subgroups. Linear regressions evaluated the relationship between CSF Ng levels, memory scores, and APOE polymorphism.
RESULTS: Ng levels were higher in aMCI-AD patients compared to MCI-FTLD (F[1, 134] = 15.16, p < .001), and in AD-dementia compared to FTLD-dementia (F[1, 96] = 4.60, p = .029). Additionally, Ng levels were higher in FTLD-dementia patients compared to MCI-FTLD (F[1, 54]= 4.35, p = .034), lower in SCD participants compared to aMCI-AD (F[1, 142] = 10.72, p = .001) and AD-dementia (F[1, 100] = 20.90, p < .001), and did not differ between SCD participants and MCI-FTLD (F[1, 58]= 1.02, p = .491) or FTLD-dementia (F[1, 62]= 2.27, p = .051). The main effect of diagnosis across the diagnostic subgroups on Aβ1-42/Ng ratio was significant too (F[4, 263]=, p < .001). We found a non-significant association between Ng levels and memory scores overall (β=-0.25, p = .154) or in AD diagnostic subgroups, and non-significant differences in this association between overall AD APOE ε4 carriers and non-carriers (β=-0.32, p = .358).
CONCLUSIONS: In this first study to-date to assess MCI and dementia due to AD or FTLD within one study, elevated CSF Ng appears to be an early biomarker of AD-related impairment, but its role as a biomarker appears to diminish after dementia diagnosis, whereby dementia-related underlying processes in AD and FTLD may begin to merge. The Aβ1-42/Ng ratio discriminated AD from FTLD patients better than Ng alone. CSF Ng levels were not related to memory in AD or FTLD, suggesting that Ng may be a marker of the biological signs of disease state rather than cognitive deficits.