2012年1月2日，據(jù)《每日科學(xué)》報道,，在患輕度認(rèn)知功能損害的患者發(fā)展為阿爾茲海默?。ˋD）癡呆癥之前，其腦脊液中Aβ42的水平似乎已經(jīng)下降了至少5至10年,，而其他的一些因子的腦脊液水平似乎是AD的遲發(fā)性標(biāo)記物,，根據(jù)1月期的Archives of General Psychiatry期刊（JAMA/Archives期刊的一種）上的一則研究報告。
研究人員指出,，如果能夠在疾病的早期階段應(yīng)用疾病修飾療法如免疫治療,，則更有可能成功。
因此有必要在神經(jīng)退行性病癥發(fā)展不是太嚴(yán)重之前鑒定出阿爾茨海默病患者,。
Peder Buchhave,，醫(yī)學(xué)博士，任職于瑞士隆德大學(xué)和斯科納大學(xué),，和同事們對以前的一個137例患輕度認(rèn)知功能障礙（MCI）的研究進(jìn)行了一個擴(kuò)展的隨訪隊列研究,，平均隨訪時間為9.2年。
在跟進(jìn)隨訪中,，72例（53.7%）患上了阿爾茲海默?。ˋD），21例（15.7%）發(fā)展成了其他形式的老年癡呆癥,。在基線水平,，與沒有發(fā)展為AD的患者相比，發(fā)展為AD的患者其腦脊液中,，Aβ42水平降低了而其他生物標(biāo)志物如T-tau和P-tau蛋白水平升高了,。
研究表明，與那些在5-10年內(nèi)轉(zhuǎn)變?yōu)锳D 的MCI患者相比,，在5年內(nèi)轉(zhuǎn)變?yōu)锳D的MCI患者中腦脊液Aβ42基線水平同等的減少了,。
研究人員預(yù)計，大約90%的患MCI和存在基線病理CSF標(biāo)記物的患者,，將在9.2年內(nèi)發(fā)展成為AD,。
"因此，這些標(biāo)記物能夠在轉(zhuǎn)變成老年癡呆癥前至少5-10年鑒別出具有患AD高風(fēng)險性的個體,。希望那些能延緩或阻止疾病的發(fā)展新的療法能夠很快問世,。結(jié)合一種早期及準(zhǔn)確的診斷，這些療法將能夠在神經(jīng)元變性還不是太普遍及患者患老年癡呆癥前發(fā)揮作用,，"作者總結(jié)道,。（生物谷bioon.com）
doi:10.1001/archgenpsychiatry.2011.155
PMC:
PMID:
Cerebrospinal Fluid Levels of -Amyloid 1-42, but Not of Tau, Are Fully Changed Already 5 to 10 Years Before the Onset of Alzheimer Dementia
P. Buchhave, L. Minthon, H. Zetterberg, A. K. Wallin, K. Blennow, O. Hansson
Context：Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease. Objectives：To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD. Design：A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years). Setting：Memory disorder clinic. Patients：A total of 137 patients with MCI who underwent lumbar puncture at baseline. Main Outcome Measure：Conversion to AD dementia. Results：During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P < .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%. Conclusions：Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration.
