Institute for Regenerative Medicine, University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland.
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, Lengstrasse 31, Zürich, Switzerland.
J Neuroinflammation. 2022 May 28;19(1):127. doi: 10.1186/s12974-022-02473-3.
Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer's disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression.
We quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) samples in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits.
NPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10-kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1.
Distinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression.
神经炎症可能导致老年人的精神症状，尤其是在阿尔茨海默病（AD）的背景下。我们试图确定与神经精神症状（NPS）相关的全身性和中枢神经系统（CNS）炎症改变；并研究它们与 AD 病理学和临床疾病进展的关系。
我们在认知正常和受损的老年受试者的配对血清和脑脊液（CSF）样本中定量了一组 38 种神经炎症和血管损伤标志物。我们进行了神经精神病学和认知评估，并测量了 CSF 中 AD 病理学的生物标志物。多变量分析确定了与 NPS 相关的血清和 CSF 神经炎症改变，考虑了认知状态、AD 病理学和随访时的认知下降。
NPS 与血清中涉及嗜酸性粒细胞趋化因子-3、白细胞介素（IL）-6 和 C 反应蛋白的不同炎症谱，以及 CSF 中涉及可溶性细胞间黏附分子-1（sICAM-1）、IL-8、10-kDa 干扰素-γ诱导蛋白和 CRP 的不同炎症谱相关。AD 病理学与 CSF sICAM-1 相互作用与 NPS 相关。表现出 NPS 与随后的认知下降相关，CSF sICAM-1 介导了这种相关性。
不同的全身性和 CNS 炎症过程参与了老年人 NPS 的病理生理学。神经炎症可能解释了 NPS 与更快的临床疾病进展之间的联系。
