Associations of Neuropsychiatric Features with Cerebrospinal Fluid Biomarkers of Amyloidogenesis and Neurodegeneration in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People
Associations of Neuropsychiatric Features with Cerebrospinal Fluid Biomarkers of Amyloidogenesis and Neurodegeneration in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People
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DOI：
10.3233/jad-210272
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发表时间：
2021-01-01
影响因子：
4
通讯作者：
Naffah-Mazzacoratti, Maria da Graca
中科院分区：
文献类型：
--
作者：
de Oliveira, Fabricio Ferreira;Miraldo, Marjorie Camara;Naffah-Mazzacoratti, Maria da Graca
背景：在神经退行性疾病中，行为特征可能反映了预测病理生理的蛋白质病变。目的：研究路易体痴呆（DLB）、晚发性阿尔茨海默病（AD）和认知健康人群中淀粉样变和神经退行性变脑脊液生物标志物与神经精神特征的关系。方法：连续门诊DLB患者按性别、痴呆分期、认知评分与AD门诊患者配对，按性别、年龄与认知健康对照组配对，根据APOE epsilon 4携带者状态，研究脑脊液淀粉样蛋白- β (A β)（42）、A β(40)、A β(38)、总tau蛋白、磷酸化tau蛋白Thr181、α -突触核蛋白、泛素和神经丝光与神经精神特征的关系。结果：总体而言，27例DLB患者（78.48 +/- 9.0岁，11例APOE epsilon 4携带者）与27例AD患者（81.00 +/- 5.8岁，12例APOE epsilon 4携带者）和27例对照组（78.48 +/- 8.7岁，4例APOE epsilon 4携带者）配对；三分之二是女性。DLB患者行为负担更重。当患者携带APOE epsilon 4等位基因时，反映DLB中淀粉样变性和神经变性的生物标志物比率与AD患者更相似。在纠正错误发现率后，以下关联仍然显著：在DLB中，烦躁不安与牛头病和淀粉样蛋白形成的间接测量相关，而在AD中，躁动和夜间行为障碍与牛头病相关，妄想与牛头病和淀粉样蛋白形成的间接测量相关。结论：当与分离的生物标志物相关性不显著时，生物标志物比率优于A β和tau生物标志物预测神经精神症状。最后，APOE ε 4载体状态影响DLB和AD的淀粉样蛋白形成和tau病理，仅影响DLB的轴突变性。
Background: Behavioral features may reflect proteinopathies predicting pathophysiology in neurodegenerative diseases.Objective: We aimed to investigate associations of cerebrospinal fluid biomarkers of amyloidogenesis and neurodegeneration with neuropsychiatric features in dementia with Lewy bodies (DLB) compared with late-onset Alzheimer's disease (AD) and cognitively healthy people.Methods: Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive scores, and with cognitively healthy controls according to sex and age to investigate associations of cerebrospinal fluid amyloid-beta (A beta)(42), A beta(40), A beta(38), total tau, phospho-tau Thr181, alpha-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOE epsilon 4 carrier status.Results: Overall, 27 patients with DLB (78.48 +/- 9.0 years old, eleven APOE epsilon 4 carriers) were paired with 27 patients with AD (81.00 +/- 5.8 years old, twelve APOE epsilon 4 carriers) and 27 controls (78.48 +/- 8.7 years old, four APOE epsilon 4 carriers); two thirds were women. Behavioral burden was more intense in DLB. Biomarker ratios reflecting amyloidogenesis and neurodegeneration in DLB were more similar to those in AD when patients carried APOE epsilon 4 alleles. After corrections for false discovery rates, the following associations remained significant: in DLB, dysphoria was associated with tauopathy and indirect measures of amyloidogenesis, while in AD, agitation, and night-time behavior disturbances were associated with tauopathy, and delusions were associated with tauopathy and indirect measures of amyloidogenesis.Conclusion: Biomarker ratios were superior to A beta and tau biomarkers predicting neuropsychiatric symptoms when associations with isolated biomarkers were not significant. At the end, APOE epsilon 4 carrier status influenced amyloidogenesis and tau pathology in DLB and in AD, and axonal degeneration only in DLB.