Mollenhauer Brit, Steinacker Petra, Bahn Erik, Bibl Mirko, Brechlin Peter, Schlossmacher Michael G, Locascio Joseph J, Wiltfang Jens, Kretzschmar Hans A, Poser Sigrid, Trenkwalder Claudia, Otto Markus
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Neurodegener Dis. 2007;4(5):366-75. doi: 10.1159/000105157. Epub 2007 Jul 6.
The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases.
We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nondemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of H-FABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis.
Serum H-FABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio > or =8 this quotient reached a sensitivity of 91% and a specificity of 66%.
Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB.
脑脊液(CSF)中生物标志物的检测在某些神经退行性疾病的诊断中越来越受到认可。心脏型脂肪酸结合蛋白(H-FABP)最近在神经退行性疾病患者的脑脊液和血清中被发现。
我们单独研究了脑脊液和血清中的H-FABP,并将其与脑脊液tau蛋白联合研究,以评估它们作为路易体痴呆(DLB)和阿尔茨海默病(AD)鉴别诊断潜在生物标志物的可能性。
我们测定了144例DLB患者(n = 33)、帕金森病痴呆(PDD;n = 25)、AD患者(n = 35)和非痴呆神经对照(NNC;n = 51)的H-FABP和tau蛋白值。此外,使用市售酶联免疫吸附测定法分析了45例无认知功能下降证据的特发性帕金森病患者的血清H-FABP水平。我们计算了脑脊液和血清中H-FABP和tau蛋白的绝对值,并确定两者之间的相对比值,以获得与临床工作诊断的最佳匹配。
与NNC和AD受试者相比,DLB和PDD患者的血清H-FABP水平升高。为了更好地区分DLB和AD,我们计算了血清H-FABP与脑脊液tau蛋白水平的比值。在任意选择的截断比值≥8时,该商数的敏感性达到91%,特异性达到66%。
我们的结果表明,脑脊液tau蛋白的检测,以及血清和脑脊液中H-FABP的定量,以及血清H-FABP与脑脊液tau蛋白的比值,代表了AD和DLB鉴别诊断的候选标志物。