Neuropathologically defined subtypes of Alzheimer's disease differ significantly from neurofibrillary tangle-predominant dementia.
Neuropathologically defined subtypes of Alzheimer's disease differ significantly from neurofibrillary tangle-predominant dementia.
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DOI：
10.1007/s00401-012-1044-y
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发表时间：
2012-11
影响因子：
12.7
通讯作者：
Murray ME
中科院分区：
文献类型：
--
作者：
Janocko NJ;Brodersen KA;Soto-Ortolaza AI;Ross OA;Liesinger AM;Duara R;Graff-Radford NR;Dickson DW;Murray ME
阿尔茨海默病(AD)可根据海马区神经原纤维缠结(NFT)和联合皮质的相对密度分为典型AD、海马区AD(HPSP AD)和边缘优势AD(LP AD)三种亚型。AD亚型不仅在病理上有差异，而且在人口学、临床和遗传上也有差异。神经纤维缠结占优势的痴呆(NFTD)是一种疾病，其NFT相对局限于边缘结构，与LP AD共享这一特征，增加了NFTD是AD变体的可能性。NFTD的病理诊断尚无客观标准。这项研究的目的是设计一种数学算法，可以根据NFT和海马区和联想皮质中的老年斑(SP)计数来诊断NFTD，类似于用于AD亚型的算法。此外，我们还比较了NFTD(n=18)和LP AD(n=19)的病理、人口学、临床和遗传学特征，以及其他AD亚型，典型AD(n=52)和HPSP AD(n=17)。利用数字显微镜，我们证实了磷酸-tau(CP13)和NFT构象表位(AB39)的负荷量与NFT密度相关，并显示出预期的AD亚型模式。皮质CP13和AB39免疫反应负荷以HPSP AD最高，LP AD最低。另一方面，皮质β-淀粉样蛋白负荷在不同AD亚型之间没有显著差异。基底节SPS的半定量评估确实显示HPSP AD的SPS出现频率明显高于典型AD，其发生率高于LP AD。与LP AD相比，NFTD起病年龄大，病程短，Braak NFT分期低。在硫代黄素-S荧光显微镜下，NFTs和SP以及CP13、AB39和Aβ在额叶皮质中的免疫反应性很低，区分了NFTD和AD亚型，包括LP和AD。NFTD组和LP AD组MAPTH1H1基因频率较高(~70%)，与典型AD相似，而NFTD组APOEε4携带者较低。虽然NFTD在女性占优势、高龄起病和认知功能减退方面有相似的临床表现，但它在病理上与LP AD有显著差异，提示它可能不仅仅是AD的一个变种。
Alzheimer’s disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (n = 18) with LP AD (n = 19), as well as the other AD subtypes, typical AD (n = 52) and HpSp AD (n = 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical β-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aβ immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70 %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.
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影响因子：
12.7
作者：
BRAAK, H;BRAAK, E
通讯作者：
BRAAK, E
影响因子：
14.5
作者：
Koivunen, J.;Verkkoniemi, A.;Rinne, J. O.
通讯作者：
Rinne, J. O.
DOI：
10.1073/pnas.92.8.3586
发表时间：
1995-04-11
影响因子：
11.1
作者：
HYMAN, BT;WEST, HL;STANLEY, HE
通讯作者：
STANLEY, HE
影响因子：
48
作者：
Murray, Melissa E.;Graff-Radford, Neill R.;Ross, Owen A.;Petersen, Ronald C.;Duara, Ranjan;Dickson, Dennis W.
通讯作者：
Dickson, Dennis W.
影响因子：
5.3
作者：
Kim, Jungsu;Miller, Victor M.;Golde, Todd E.
通讯作者：
Golde, Todd E.