路易体痴呆与阿尔茨海默病及认知健康人群相比，神经精神特征与淀粉样蛋白生成和神经退行性变的脑脊液生物标志物的相关性。

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.

机构信息

Department of Neurology and Neurosurgery Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

出版信息

J Alzheimers Dis. 2021;81(3):1295-1309. doi: 10.3233/JAD-210272.

DOI:10.3233/JAD-210272

PMID:33935098

Abstract

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-β (Aβ)42, Aβ40, Aβ38, total tau, phospho-tau Thr181, α-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOEɛ4 carrier status.

RESULTS

Overall, 27 patients with DLB (78.48±9.0 years old, eleven APOEɛ4 carriers) were paired with 27 patients with AD (81.00±5.8 years old, twelve APOEɛ4 carriers) and 27 controls (78.48±8.7 years old, four APOEɛ4 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 APOEɛ4 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 Aβ and tau biomarkers predicting neuropsychiatric symptoms when associations with isolated biomarkers were not significant. At the end, APOEɛ4 carrier status influenced amyloidogenesis and tau pathology in DLB and in AD, and axonal degeneration only in DLB.

摘要

背景

行为特征可能反映出预测神经退行性疾病病理生理学的蛋白病。

目的

我们旨在研究与阿尔茨海默病（AD）相比，路易体痴呆（DLB）患者的脑脊液淀粉样蛋白生成和神经退行性生物标志物与神经精神特征的关联，并与认知健康的个体进行比较。

方法

连续入组的 DLB 门诊患者根据性别、痴呆阶段和认知评分与 AD 门诊患者进行配对，根据性别和年龄与认知健康对照进行配对，以调查脑脊液淀粉样蛋白-β（Aβ）42、Aβ40、Aβ38、总tau、磷酸化 tau Thr181、α-突触核蛋白、泛素和神经丝轻链与神经精神特征的关联，并根据载脂蛋白 Eɛ4 等位基因进行分析。

结果

共有 27 例 DLB 患者（78.48±9.0 岁，11 例载脂蛋白 Eɛ4 携带者）与 27 例 AD 患者（81.00±5.8 岁，12 例载脂蛋白 Eɛ4 携带者）和 27 例对照（78.48±8.7 岁，4 例载脂蛋白 Eɛ4 携带者）配对；三分之二为女性。DLB 患者的行为负担更重。当患者携带载脂蛋白 Eɛ4 等位基因时，DLB 患者的淀粉样蛋白生成和神经退行性生物标志物比值与 AD 患者更相似。在进行假发现率校正后，以下关联仍然显著：在 DLB 中，情绪低落与 tau 病和淀粉样蛋白生成的间接标志物相关，而在 AD 中，激越和夜间行为障碍与 tau 病相关，妄想与 tau 病和淀粉样蛋白生成的间接标志物相关。