不同认知衰退水平个体的脑脊液生物标志物谱的异质性：一项横断面研究。

Heterogeneity of Cerebrospinal Fluid Biomarkers Profiles in Individuals with Distinct Levels of Cognitive Decline: A Cross-Sectional Study.

机构信息

Laboratory of Neuroscience, Departamento e Instituto de Psiquiatria HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.

Instituto Nacional de Biomarcadores em Neuropsiquiatria (InBion), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Sao Paulo, Brazil.

出版信息

J Alzheimers Dis. 2021;81(3):949-962. doi: 10.3233/JAD-210144.

DOI:10.3233/JAD-210144

PMID:33843685

Abstract

BACKGROUND

Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer's disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice.

OBJECTIVE

To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment.

METHODS

204 participants were enrolled for a cross-sectional assessment and allocated into diagnostic groups: probable AD (n = 60, 29.4%); MCI (n = 84, 41.2%); or normal cognition (NC, n = 60, 29.4%). CSF concentrations of Aβ42, T-tau, and 181Thr-P-tau were determined, and Aβ42/P-tau ratio below 9.53 was used as a proxy of AD pathology. The AT(N) classification was further used as a framework to ascertain the biological evidence of AD.

RESULTS

The majority (73.7%) of patients in the AD group had the Aβ42/P-tau ratio below the cut-off score for AD, as opposed to a smaller proportion in the MCI (42.9%) and NC (23.3%) groups. In the latter, 21 subjects (35%) were classified as A+, 28 (46.7%) as T+, and 23 (38.3%) as N + . In the AD group, 66.7%of the cases were classified as A+, 78.3%as T+, and 80%as N+.

CONCLUSION

Analysis of CSF biomarkers was able to discriminate between AD, MCI, and NC. However, clinical-biological mismatches were observed in a non-negligible proportion of cases.

摘要

背景

脑脊液（CSF）中淀粉样蛋白-β（Aβ）浓度降低，总（T-tau）和磷酸化 tau 蛋白（P-tau）升高，被广泛认为是阿尔茨海默病（AD）病理的核心生物标志物。尽管如此，仍有一些需要注意的问题，这使得 AD 生物标志物尚未完全纳入临床实践。

目的

确定认知障碍程度不同的老年临床样本中临床-生物学不匹配的频率。

方法

204 名参与者进行了横断面评估，并分配到诊断组：可能的 AD（n=60，29.4%）；MCI（n=84，41.2%）；或正常认知（NC，n=60，29.4%）。测定 CSF 中 Aβ42、T-tau 和 181Thr-P-tau 的浓度，Aβ42/P-tau 比值低于 9.53 被用作 AD 病理的替代物。进一步使用 AT（N）分类作为确定 AD 生物学证据的框架。

结果

AD 组中大多数（73.7%）患者的 Aβ42/P-tau 比值低于 AD 的截止值，而 MCI（42.9%）和 NC（23.3%）组的比例较小。在后一组中，有 21 名受试者（35%）被归类为 A+，28 名（46.7%）为 T+，23 名（38.3%）为 N+。在 AD 组中，66.7%的病例被归类为 A+，78.3%为 T+，80%为 N+。