Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Department of Dermatology, Karolinska University Hospital, Solna, Sweden.
Alzheimers Res Ther. 2020 Nov 17;12(1):153. doi: 10.1186/s13195-020-00718-y.
The underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia.
A total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer's disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1-42, Ng, NFL, and GAP-43.
No significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS.
Our results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.
神经精神症状（NPS）在痴呆中的潜在发病机制尚不清楚。脑脊液（CSF）中突触和轴突变性的生物标志物可能为其发生提供新的神经病理学信息。本研究旨在探讨痴呆患者 NPS 与 CSF 中突触（神经颗粒蛋白 [Ng]、生长相关蛋白 43 [GAP-43]）和轴突（神经丝轻链 [NFL]）损伤生物标志物之间的关系。
共纳入 151 例患者（平均年龄 ± 标准差，73.5 ± 11.0 岁；女性 n = 92 [61%]），其中 64 例为阿尔茨海默病（AD）患者（34 例 NPS 较高，即神经精神病学问卷（NPI）评分 > 10，30 例 NPS 较低），18 例为血管性痴呆（VaD）患者，27 例为混合性痴呆（MIX）患者，12 例为轻度认知障碍（MCI）患者，30 例为主观认知障碍（SCI）患者。主要使用 NPI 评估 NPS。使用酶联免疫吸附测定（ELISA）法分析 CSF 样本中的 T-tau、P-tau、Aβ1-42、Ng、NFL 和 GAP-43。
AD 患者中，NPS 较高与较低组之间的 CSF Ng、GAP-43 和 NFL 水平无显著差异（但 AD 患者中<70 岁且 NPS 较高者的 Ng 水平几乎显著降低，p = 0.06）。AD 患者中 NPS 与 CSF 生物标志物之间无显著相关性。在 VaD 患者（n = 17）中，GAP-43、Ng、NFL 和 NPS 之间存在负相关。
我们的结果表明，在 AD 连续体早期（年龄 < 70 岁），较低水平的 Ng 可能与 NPS 的严重程度较高有关。此外，我们的数据可能表明，在 VaD 病理情况下，NPS 的存在与突触和轴突变性之间存在潜在关系。
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