{"title":"反式反应DNA结合蛋白在阿尔茨海默病海马病理学中的独特模式 43","authors":"Grace Minogue BA, Allegra Kawles BA, Antonia Zouridakis BS, Rachel Keszycki MS, Alyssa Macomber BS, Vivienne Lubbat, Nathan Gill PhD, Qinwen Mao MD, Margaret E. Flanagan MD, Hui Zhang PhD, Rudolph Castellani MD, Eileen H. Bigio MD, M.-Marsel Mesulam MD, Changiz Geula PhD, Tamar Gefen PhD","doi":"10.1002/ana.26762","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A total of 48 extensively characterized cases (14 AD, 16 AD/TDP, 18 FTLD-TDP) were analyzed using digital HALO software (Indica Labs, Albuquerque, NM, USA) to quantify pathological burden and neuronal loss.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In AD/TDP and FTLD-TDP, TDP-43 immunoreactivity was greatest in the DG. Tau immunoreactivity was significantly greater in DG and CA3 in AD/TDP compared with pure AD. All clinical groups showed the highest amounts of neurons in DG, followed by CA3, then CA1. The AD and AD/TDP groups showed lower neuronal counts compared with the FTLD-TDP group across all hippocampal subregions consistent with the salience of the amnestic phenotype.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>We conclude that AD/TDP can be distinguished from AD and FTLD-TDP based on differential regional distributions of hippocampal tau and TDP-43. Findings suggest that tau aggregation in AD/TDP might be enhanced by TDP-43. ANN NEUROL 2023;94:1036–1047</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 6","pages":"1036-1047"},"PeriodicalIF":8.1000,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26762","citationCount":"0","resultStr":"{\"title\":\"Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43\",\"authors\":\"Grace Minogue BA, Allegra Kawles BA, Antonia Zouridakis BS, Rachel Keszycki MS, Alyssa Macomber BS, Vivienne Lubbat, Nathan Gill PhD, Qinwen Mao MD, Margaret E. Flanagan MD, Hui Zhang PhD, Rudolph Castellani MD, Eileen H. Bigio MD, M.-Marsel Mesulam MD, Changiz Geula PhD, Tamar Gefen PhD\",\"doi\":\"10.1002/ana.26762\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>A total of 48 extensively characterized cases (14 AD, 16 AD/TDP, 18 FTLD-TDP) were analyzed using digital HALO software (Indica Labs, Albuquerque, NM, USA) to quantify pathological burden and neuronal loss.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In AD/TDP and FTLD-TDP, TDP-43 immunoreactivity was greatest in the DG. Tau immunoreactivity was significantly greater in DG and CA3 in AD/TDP compared with pure AD. All clinical groups showed the highest amounts of neurons in DG, followed by CA3, then CA1. The AD and AD/TDP groups showed lower neuronal counts compared with the FTLD-TDP group across all hippocampal subregions consistent with the salience of the amnestic phenotype.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>We conclude that AD/TDP can be distinguished from AD and FTLD-TDP based on differential regional distributions of hippocampal tau and TDP-43. Findings suggest that tau aggregation in AD/TDP might be enhanced by TDP-43. ANN NEUROL 2023;94:1036–1047</p>\\n </section>\\n </div>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":\"94 6\",\"pages\":\"1036-1047\"},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2023-08-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26762\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ana.26762\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ana.26762","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43
Objective
Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).
Methods
A total of 48 extensively characterized cases (14 AD, 16 AD/TDP, 18 FTLD-TDP) were analyzed using digital HALO software (Indica Labs, Albuquerque, NM, USA) to quantify pathological burden and neuronal loss.
Results
In AD/TDP and FTLD-TDP, TDP-43 immunoreactivity was greatest in the DG. Tau immunoreactivity was significantly greater in DG and CA3 in AD/TDP compared with pure AD. All clinical groups showed the highest amounts of neurons in DG, followed by CA3, then CA1. The AD and AD/TDP groups showed lower neuronal counts compared with the FTLD-TDP group across all hippocampal subregions consistent with the salience of the amnestic phenotype.
Interpretation
We conclude that AD/TDP can be distinguished from AD and FTLD-TDP based on differential regional distributions of hippocampal tau and TDP-43. Findings suggest that tau aggregation in AD/TDP might be enhanced by TDP-43. ANN NEUROL 2023;94:1036–1047
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
