Justo Alberto Fernando Oliveira, Toscano Eliana Cristina de Brito, Goncalves Natalia Gomes, Leite Renata Elaine Paraízo, Paes Vitor Ribeiro, Nitrini Ricardo, Pasqualucci Carlos, Lin Chin Jia, Grinberg Lea T, Suemoto Claudia Kimie
Division of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, São Paulo, Brazil.
Physiopathology in Laboratory (LIM-22), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Neurochem Res. 2025 Jun 12;50(3):197. doi: 10.1007/s11064-025-04444-5.
Alzheimer's disease (AD) neuropathological changes (ADNC) are characterized by amyloid plaques and neurofibrillary tangles. The role of nitric oxide synthase (NOS) in disease progression remains unclear. This study investigates the expression of neural, inducible, and endothelial NOS (nNOS, iNOS, eNOS) and 3-nitrotyrosine (3-NT) in the hippocampal subregions of individuals with ADNC and their association with cognitive abilities. Immunohistochemistry was performed on hippocampal samples from 10 individuals with ADNC and 10 age- and sex-matched controls to detect NOS enzymes, and 3-NT expression in CA1, CA2, CA3, and CA4. Logistic ordinal regressions evaluated associations of NOS and 3-NT expression with AD pathology, while linear regressions assessed relationships with cognitive abilities. Overexpression of nNOS was observed in all hippocampal subregions in ADNC participants. iNOS expression was elevated in CA1 and CA3, while eNOS showed increased levels only in CA3. 3-NT was significantly higher in CA3 of ADNC participants. nNOS expression in all hippocampal regions correlated with AD pathology and cognitive impairment. iNOS in CA3 was associated with AD pathology and cognitive scores. No associations were found for eNOS, and 3-NT in CA3 correlated with cognitive impairment. Associations of nNOS and iNOS with neuropathology and cognition suggest a role for NOS in AD pathophysiology.
阿尔茨海默病（AD）神经病理改变（ADNC）的特征是淀粉样斑块和神经原纤维缠结。一氧化氮合酶（NOS）在疾病进展中的作用仍不清楚。本研究调查了患有ADNC个体海马亚区中神经型、诱导型和内皮型NOS（nNOS、iNOS、eNOS）以及3-硝基酪氨酸（3-NT）的表达情况，及其与认知能力的关联。对10例患有ADNC的个体以及10例年龄和性别匹配的对照者的海马样本进行免疫组织化学检测，以检测NOS酶以及CA1、CA2、CA3和CA4区域中3-NT的表达。逻辑序数回归评估了NOS和3-NT表达与AD病理学的关联，而线性回归评估了与认知能力的关系。在患有ADNC的参与者的所有海马亚区均观察到nNOS的过表达。CA1和CA3区域的iNOS表达升高，而eNOS仅在CA3区域显示水平增加。患有ADNC的参与者CA3区域的3-NT显著更高。所有海马区域的nNOS表达与AD病理学和认知障碍相关。CA3区域的iNOS与AD病理学和认知评分相关。未发现eNOS存在关联，且CA3区域的3-NT与认知障碍相关。nNOS和iNOS与神经病理学和认知的关联表明NOS在AD病理生理学中发挥作用。
