Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer's disease: An autopsy-confirmed study.
Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer's disease: An autopsy-confirmed study.
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DOI：
10.1371/journal.pone.0171524
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Murayama S
中科院分区：
文献类型：
--
作者：
Morimoto S;Takao M;Hatsuta H;Nishina Y;Komiya T;Sengoku R;Nakano Y;Uchino A;Sumikura H;Saito Y;Kanemaru K;Murayama S
路易体痴呆（DLB）和阿尔茨海默病（AD）是痴呆的两种最常见原因。两种病理经常共存，并且与单纯 AD 患者相比，伴有新皮质 LB 病理的 AD 患者（称为 AD 的路易体变体）通常表现出更快的认知衰退和加速的死亡率。因此，区分 DLB、AD 以及同时患有 DLB 和 AD 的患者在临床实践中非常重要。我们检测了脑脊液 (CSF) 中高香草酸 (HVA)、5-羟基吲哚乙酸 (5-HIAA)、tau、磷酸化 tau (p-tau) 和 β-淀粉样蛋白 (Aβ) 1-42 的水平，以评估它们作为区分不同形式痴呆的生物标志物的可行性。我们从1996年至2015年期间，从我院收治的患者中总共获取了3498份脑脊液样本。其中，我们能够对94例患者进行脑部尸检。最后，对 78 例神经病理诊断病例（10 例 AD、6 例 DLB、5 例 DLB 合并 AD、5 例无神经系统疾病的对照例、52 例患有其他神经系统疾病）进行了研究。与病理初期 LBD（Braak LB 阶段 <2）相比，病理晚期路易体疾病（LBD；Braak LB 阶段 >3）CSF 中 HVA 和 5-HIAA 水平持续降低。这些结果表明，如果个体的中枢神经系统患有 LB 病理，则临床症状出现后 CSF 中的 HVA 和 5-HIAA 水平可能会降低。此外，脑脊液中 HVA 和 5-HIAA 水平随 LB 病理变化而降低，在 DLB 和伴有 AD 的 DLB 病例中尤其低。此外，CSF 中的 HVA、5-HIAA 和脑特异性蛋白 t-tau、p-tau 和 Aβ 1-42 的组合有助于区分 DLB、DLB 合并 AD 以及具有高诊断准确性的 AD。
Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1–42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia. We obtained a total of 3498 CSF samples from patients admitted to our hospital during the period from 1996 to 2015. Of these patients, we were able to carry out a brain autopsy in 94 cases. Finally, 78 neuropathologically diagnosed cases (10 AD, six DLB, five DLB with AD, five controls without neurological diseases, and 52 cases with other neurological diseases) were studied. CSF levels of HVA and 5-HIAA were consistently decreased in pathologically advanced Lewy body disorder (LBD; Braak LB stages >3) compared with pathologically incipient LBD (Braak LB stages <2). These results suggest that if an individual has LB pathology in the central nervous system, CSF levels of HVA and 5-HIAA may decrease after the onset of clinical symptoms. In addition, CSF levels of HVA and 5-HIAA decreased with LB pathology, and were especially low in cases of DLB and DLB with AD. Furthermore, the combination of HVA, 5-HIAA, and brain specific proteins t-tau, p-tau, and Aβ 1–42 in CSF were useful for discriminating among DLB, DLB with AD, and AD with high diagnostic accuracy.