Memory Clinic, Department of Neurology, Second Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic.
Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ, USA.
Alzheimers Res Ther. 2024 Sep 6;16(1):199. doi: 10.1186/s13195-024-01566-w.
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.
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.
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 Aβ/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).
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 Aβ/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.
有初步证据表明，生物标志物神经颗粒蛋白（Ng）可能有助于将阿尔茨海默病（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 与额颞叶变性（FTLD）病理以及同一疾病不同阶段的能力；（b）Ng 水平与 AD 和 FTLD 病理中认知表现的关系；（c）CSF Ng 水平是否因载脂蛋白 E（APOE）多态性在 AD 连续体中发生变化。
我们招募了来自捷克大脑老化研究的主观认知下降（SCD）（n=33）、AD 所致遗忘型轻度认知障碍（aMCI）（n=109）、AD 痴呆（n=67）、FTLD 所致 MCI（n=25）和 FTLD 痴呆（n=29）患者。单因素方差分析（ANCOVA）评估了诊断亚组中的 Ng 水平。线性回归评估了 CSF Ng 水平、记忆评分和 APOE 多态性之间的关系。
与 MCI-FTLD 相比，aMCI-AD 患者的 Ng 水平更高（F[1, 134]=15.16，p<0.001），与 FTLD 相比，AD 痴呆患者的 Ng 水平更高（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=0.034），与 SCD 相比，aMCI-AD 患者的 Ng 水平更低（F[1, 142]=10.72，p=0.001）和 AD 痴呆患者的 Ng 水平更低（F[1, 100]=20.90，p<0.001），而与 MCI-FTLD 患者的 Ng 水平无差异（F[1, 58]=1.02，p=0.491）或与 FTLD 痴呆患者的 Ng 水平无差异（F[1, 62]=2.27，p=0.051）。诊断亚组中 Aβ/Ng 比值的主要诊断效果也很显著（F[4, 263]=，p<0.001）。我们发现，Ng 水平与总体记忆评分之间存在非显著关联（β=-0.25，p=0.154）或在 AD 诊断亚组中存在非显著关联，并且在 AD 总体 APOE ε4 携带者和非携带者之间，这种关联没有显著差异（β=-0.32，p=0.358）。
在迄今为止评估 AD 或 FTLD 所致 MCI 和痴呆的第一项研究中，升高的 CSF Ng 似乎是 AD 相关损伤的早期生物标志物，但在痴呆诊断后，其作为生物标志物的作用似乎会减弱，AD 和 FTLD 中与痴呆相关的潜在过程可能开始融合。Aβ/Ng 比值比 Ng 单独检测能更好地区分 AD 和 FTLD 患者。CSF Ng 水平与 AD 或 FTLD 中的记忆无关，表明 Ng 可能是疾病状态的生物学标志物，而不是认知缺陷。
