Andersson Christin, Blennow Kaj, Almkvist Ove, Andreasen Niels, Engfeldt Peter, Johansson Sven-Erik, Lindau Maria, Eriksdotter-Jönhagen Maria
Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, NOVUM Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
Neurobiol Aging. 2008 Oct;29(10):1466-73. doi: 10.1016/j.neurobiolaging.2007.03.027. Epub 2007 May 23.
Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression.
To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline.
Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM).
There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up.
Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
关于神经退行性疾病进展过程中认知功能下降时脑脊液(CSF)生物标志物的纵向变化,人们了解甚少。
研究认知功能下降期间脑脊液生物标志物——总tau蛋白(T-tau)、磷酸化tau蛋白(P-tau)和β-淀粉样蛋白(Aβ42)——的纵向变化。
40名记忆门诊患者(女性占47.5%),年龄61.3±7.6(标准差)岁,基线时无痴呆,接受了两次腰椎穿刺和神经心理学测试。基线平均简易精神状态检查表(MMSE)评分28.3±1.8。根据基线记忆功能将患者分为三组:严重受损组(SIM)、中度受损组(MIM)和未受损组(NIM)。
随访期间,SIM组的P-tau显著增加,而MIM组和NIM组的P-tau没有变化。83%的SIM组患者转变为痴呆(80%为阿尔茨海默病),而大多数MIM组和NIM组患者仍未患痴呆。随访期间,任何记忆组的T-tau和Aβ42水平均未改变。
认知功能下降和转变为痴呆期间P-tau水平升高表明,P-tau可能作为神经退行性过程的纵向标志物。