阿爾茨海默癥(AD)是主要的神經(jīng)退行性疾病之一,，全球數(shù)百萬(wàn)人因該疾病而受到不同程度的影響,。尋找新的,、更精確的診斷方法對(duì)于該疾病的早期診斷尤為關(guān)鍵,。
近日,，Pravat K. Mandal博士和他的同事們共同研究開(kāi)發(fā)出一種完全無(wú)創(chuàng)的大腦成像技術(shù),，利用該技術(shù)可以測(cè)出腦內(nèi)某些特殊化學(xué)物質(zhì)的變化，這為病變于大腦海馬區(qū)AD的早期診斷拉開(kāi)了序曲,。研究論文發(fā)表于《阿爾茨海默癥》雜志(Journal of Alzheimer's Disease),。
聯(lián)合了印度Gurgaon國(guó)家大腦研究中心和約翰霍普金斯大學(xué)醫(yī)學(xué)院共同參與此項(xiàng)研究的Mandal說(shuō)：“在高齡人群中，阿爾茨海默癥(AD)已經(jīng)變成了一場(chǎng)無(wú)聲的海嘯,，悄悄席卷而來(lái),。這項(xiàng)新開(kāi)發(fā)的診斷技術(shù)無(wú)需傳統(tǒng)的血液檢測(cè),，也不用接受放射性檢查，整個(gè)過(guò)程只需不超過(guò)五分鐘即可完成,，因此很有可能給諸多的AD患者及其家庭帶來(lái)新的希望和福音,。”
Mandal和他的合作研究者運(yùn)用三維31P磁共振波譜分析(MRS)成像以及一種先進(jìn)的分析儀器研究了正常對(duì)照組、AD患者組,、輕微認(rèn)知功能障礙(MCI)患者組的大腦,，分別對(duì)他們的大腦海馬區(qū)化學(xué)物質(zhì)變化做了評(píng)估分析。他們觀察到在實(shí)施研究的過(guò)程中,，AD患者的左側(cè)海馬變成堿性,，而正常年齡增長(zhǎng)者當(dāng)中這一結(jié)果卻恰恰相反，他們的海馬趨向于更酸性,。
Mandal博士和他的同事們除此之外還確定了另外四種改變的大腦化學(xué)物質(zhì),，與正常對(duì)照組相比，在阿爾茨海默癥病變前患者和阿爾茨海默癥患者當(dāng)中,，這四種蛋白有顯著的改變,。這四種蛋白分別為磷酸單酯 (PME)——神經(jīng)元膜的構(gòu)成成分；磷酸二酯(PDE)——神經(jīng)元膜的降解產(chǎn)物,；磷酸肌酸(PCr)——為腦功能儲(chǔ)備能量,；以及三磷酸腺苷(-ATP)——大腦的能量源泉。他們的研究發(fā)現(xiàn)在這些病人中的左側(cè)海馬區(qū),，其PME水平顯著下降,，而PDE，PCr和-ATP含量水平則增加,。
Mandal博士解釋說(shuō)：“伴隨著左側(cè)海馬區(qū)PDE,，PCr和-ATP的增加以及PDE含量水平的下降，左側(cè)海馬區(qū)PH增加至堿性范圍內(nèi),，因此這些物質(zhì)有可能成為新的AD診斷生物標(biāo)記物,。”他和他的同事們計(jì)劃下一步對(duì)大樣本的阿爾茨海默癥和帕金森病例實(shí)施新的縱向研究，以進(jìn)一步確定他們目前檢測(cè)手段的特異性,。“這樣的臨床研究也正是我們所期望的,，我們希望能借助這一頂尖水準(zhǔn)級(jí)的最新檢測(cè)手段能夠較早診斷或更準(zhǔn)確地預(yù)測(cè)AD，這些也許能夠給認(rèn)知功能受損的病人帶來(lái)新的希望,。”（生物谷Bioon.com）
doi:10.3233/JAD-2012-120166
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Mapping of Hippocampal pH and Neurochemicals from in vivo Multi-Voxel 31P Experiments in Healthy Normal Young Male/Female, Mild Cognitive Impairment, and Alzheimer's Disease
Pravat K. Mandal1, Himanshu Akolkar1, Manjari Tripathi2
Magnetic resonance spectroscopy (MRS) plays an important role in the understanding of membrane and energy metabolism. The outcome of MRS experiments helps to derive important cellular conditions (e.g., intracellular pH, energy, membrane metabolism, etc.), which are directly related to neuronal health. We present a novel multi-voxel 31P MRS imaging experimental scheme along with an advanced 31P signal processing technique to determine the pH and neurochemicals from both hippocampal areas in shorter time (13.2 min) for subjects (e.g. healthy young male/female, mild cognitive impairment (MCI) and Alzheimer's disease (AD)). Significant (p = 0.005) decrease of phosphomonoester (PME) and increase of phosphodiester (PDE) (p < 0.001), γ-ATP (0.008), and PCr (p = 0.001) levels in the left hippocampus of AD patients (n = 6) compared to the control subjects (n = 12) were found based on post-hoc ANOVA. On the other hand, in the right hippocampus, decrease in PME (p = 0.008) and increase in PDE (p < 0.001) were significant between AD patients and controls. In case of AD subjects, pH in the left hippocampus is increased towards alkaline side compared to MCI but did not reach statistical significance level. The pH (left hippocampus) in AD is found to be negatively correlated (r = ?0.829, p = 0.042) with PCr level (left hippocampus) in AD subjects. In the left hippocampus, the increase in pH to alkaline range (in normal aging, pH is decreased to acidic range) along with statistically significant increments of PCr, γ-ATP, and PDE as well as decrease of PME in AD subjects provide extremely crucial clinical information, which can be used as biomarker for AD and potentially aid in the diagnosis.
