Granular expression of prolyl-peptidyl isomerase PIN1 is a constant and specific feature of Alzheimer's disease pathology and is independent of tau, Aβ and TDP-43 pathology.
Granular expression of prolyl-peptidyl isomerase PIN1 is a constant and specific feature of Alzheimer's disease pathology and is independent of tau, Aβ and TDP-43 pathology.
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DOI：
10.1007/s00401-011-0798-y
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发表时间：
2011-05
影响因子：
12.7
通讯作者：
Mann DM
中科院分区：
文献类型：
--
作者：
Dakson A;Yokota O;Esiri M;Bigio EH;Horan M;Pendleton N;Richardson A;Neary D;Snowden JS;Robinson A;Davidson YS;Mann DM
阿尔茨海默病（AD）表现为进行性记忆丧失、空间意识和运动技能下降。神经元缠结（NFT）代表AD的病理学标志之一。以前的研究表明，脯氨酰肽基顺反异构酶PIN 1 [与NIMA（从未在有丝分裂A中）-1相互作用的蛋白质]识别过度磷酸化的tau（在NFT中）并促进其去磷酸化，从而恢复其功能。本研究旨在确定PIN 1免疫反应性的频率、严重程度和分布及其与NFT和其他神经退行性病变的神经病理学标志物（如淀粉样蛋白-β（Aβ）斑块和Mr 43 kDa的转录响应性DNA结合蛋白（TDP-43））的关系。194例乳腺癌的免疫组化分析（AD 46例，帕金森病/路易体痴呆43例，进行性核上性麻痹/皮质基底节变性12例，额颞叶变性36例，与所有诊断组相比，21例运动神经元疾病和34例非痴呆（ND）个体）显示AD中PIN 1免疫反应性包涵体的频率和严重程度增加（P < 0.001）。海马和皮质的PIN 1颗粒的分布与NFT、Aβ和TDP-43病理的分布不同，尽管PIN 1免疫反应性神经元的频率随着NFT病理的增加而增加。随着AD型病变程度的加重，ND患者PIN 1表达呈进行性增高趋势。目前的研究结果表明，PIN 1变化是AD病理学的一个恒定特征，可以作为独立于tau或Aβ的AD神经病理学发作或扩散的生物标志物。
Alzheimer’s disease (AD) manifests with progressive memory loss and decline of spatial awareness and motor skills. Neurofibrillary tangles (NFTs) represent one of the pathological hallmarks of AD. Previous studies suggest that the enzyme prolyl-peptidyl cis–trans isomerase PIN1 [protein interacting with NIMA (never in mitosis A)-1] recognizes hyperphosphorylated tau (in NFTs) and facilitates its dephosphorylation, thereby recovering its function. This study aims to determine the frequency, severity and distribution of PIN1 immunoreactivity and its relationship to NFTs and other neuropathological markers of neurodegeneration such as amyloid-β (Aβ) plaques and transcription-responsive DNA-binding protein of Mr 43 kDa (TDP-43). Immunohistochemical analysis of 194 patients (46 with AD, 43 with Parkinson’s disease/dementia with Lewy bodies, 12 with progressive supranuclear palsy/corticobasal degeneration, 36 with frontotemporal lobar degeneration, 21 with motor neuron disease and 34 non-demented (ND) individuals) revealed an increased frequency and severity of PIN1 immunoreactive inclusions in AD as compared to all diagnostic groups (P < 0.001). The hippocampal and cortical distribution of PIN1 granules was distinct from that of NFTs, Aβ and TDP-43 pathologies, though the frequency of neurons with PIN1 immunoreactivity increased with increasing NFT pathology. There was a progressive increase in PIN1 changes in ND individuals as the degree of AD-type pathological changes increased. Present findings indicate that PIN1 changes are a constant feature of AD pathology and could serve as a biomarker of the onset or spread of AD neuropathology independent of tau or Aβ.
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影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
12.7
作者：
Davidson, Yvonne;Amin, Hanan;Mann, David M. A.
通讯作者：
Mann, David M. A.
影响因子：
12.7
作者：
Holzer, M;Gärtner, U;Arendt, T
通讯作者：
Arendt, T
影响因子：
5.3
作者：
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通讯作者：
Thorpe, Julian Robert
影响因子：
9.9
作者：
ARRIAGADA, PV;GROWDON, JH;HYMAN, BT
通讯作者：
HYMAN, BT