Neuropathological changes underlying clinical heterogeneity in Alzheimer disease

阿尔茨海默病临床异质性背后的神经病理学变化

• 批准号: 10631130
• 负责人: Lea Tenenholz Grinberg
• 金额: $ 18.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631130
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease therapy; Amnestic Disorder; Amyloid beta-Protein; Area; Atrophic; Automobile Driving; Autopsy; Biological; Brain; Brain region; California; Cells; Cessation of life; Clinical; Clinical Research; Cognitive; Cohort Studies; Collaborations; Collection; Data; Data Analyses; Dedications; Dementia; Disease; Epidemiology; Faculty; Functional disorder; Funding; Genetic; Goals; Grant; Heterogeneity; Hippocampal Formation; Human; Immunofluorescence Immunologic; Impaired cognition; In Situ Hybridization; Individual; Infrastructure; International; Interruption; Intrinsic factor; Lesion; Libraries; Longitudinal cohort study; Machine Learning; Manuscripts; Maps; Medical Students; Memory; Mentors; Metabolic; Methods; Mid-Career Clinical Scientist Award (K24); Molecular; Neocortex; Neuroanatomy; Neurobiology; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuroglia; Neurologist; Neurons; Pathologic; Pathology; Pathway interactions; Pattern; Persons; Phenotype; Populations at Risk; Preparation; Prevention; Primary Progressive Aphasia; Productivity; Protocols documentation; Regional Disease; Research; Research Personnel; Role; San Francisco; Symptoms; Syndrome; Testing; Time; Tissue Sample; Tissues; Training; Training Programs; Transcript; United States National Institutes of Health; Universities; University resources; Variant; Work; Writing; age related; association cortex; asymptomatic Alzheimer' s disease; behavioral variant frontotemporal dementia; brain tissue; career; cerebral atrophy; clinical heterogeneity; comorbidity; corticobasal syndrome; differential expression; effective therapy; experience; extracellular; hands on research; human RNA sequencing; innovation; interdisciplinary approach; mid-career faculty; multidisciplinary; neocortical; neuron loss; neuronal patterning; neuropathology; neurotoxicity; novel; novel marker; patient oriented; prevent; programs; recruit; regional difference; research study; residence; single nucleus RNA-sequencing; tau Proteins; tau aggregation

Project Summary This is an application for K24 award renewal for Dr. Lea T. Grinberg, a neuropathologist at the University of California, San Francisco (UCSF). Dr. Grinberg is an Associate Professor in Residence and co-lead the UCSF/Memory and Aging Center's Neuropathology Core. She is an established researcher in the patient- oriented clinical research of dementia. A distinctive hallmark of her research is her direct involvement in creating, managing, and analyzing well-characterized postmortem collections of brains belonging to people at-risk or already with dementia. Dr. Grinberg proposes to use K24 dedicated time to mentor USCF as well as international investigators in patient-oriented dementia research. Her mentees will gain hands-on research experience, expertise in age-related human neuropathology, training in data analysis, manuscript preparation, and grant writing, as well as career, mentoring. Mentee training will leverage the infrastructure and resources of the UCSF/Memory and Aging Center Autopsy program, which is part of ongoing longitudinal cohort studies, research portfolio, and her collaborations with multidisciplinary researchers in the areas of dementia domestically and worldwide. Dr. Grinberg intends to conduct K24-supported Alzheimer's disease research studies that will serve as training vehicles for mentees and expand her research. These studies, using clinical, genetic, and neuropathological data, will be conducted using data from ongoing UCSF/Memory and Aging Center's NIH- funded cohort studies of persons with Alzheimer's disease (AD). She will examine the factors underlying selective neuronal vulnerability in AD. In summary, this K24 will enhance Dr. Ginberg's active research program with extensive infrastructure at UCSF to support her goal to remain a leader in neurodegenerative diseases, especially in the field of neuropathology, and to develop a program of excellence for training medical students, trainees, and junior faculty in POR related to age-related neuropathology that is also intended to close the gaps caused by interruption of neuropathology training for neurologists and neurodegenerative disease training for neuropathologists.

项目摘要 这是莱亚T博士的K24奖励更新申请。格林伯格是密歇根大学的神经病理学家， 加州，旧金山弗朗西斯科（加州大学旧金山分校）。格林伯格是一个副教授在驻地和共同领导的 加州大学旧金山分校/记忆和衰老中心的神经病理学核心。她是一位在患者身上建立起来的研究人员- 面向痴呆症的临床研究。她的研究的一个独特标志是她直接参与创造， 管理和分析属于高危人群或 已经患有痴呆症了Grinberg博士建议使用K24专用时间来指导USCF以及国际 以病人为导向的痴呆症研究的研究者。她的学员将获得实践研究经验， 年龄相关的人类神经病理学专业知识，数据分析培训，手稿准备和资助 写作，职业生涯，指导。学员培训将利用 UCSF/记忆和衰老中心尸检计划，这是正在进行的纵向队列研究的一部分，研究 投资组合，以及她与国内痴呆症领域的多学科研究人员的合作， 国际吧Grinberg博士打算进行K24支持的阿尔茨海默病研究， 作为学员的培训工具，并扩大她的研究。这些研究，使用临床，遗传， 神经病理学数据，将使用正在进行的UCSF/记忆和衰老中心的NIH- 资助的阿尔茨海默病（AD）患者队列研究。她将研究选择性的潜在因素， AD中的神经元脆弱性。总之，K24将加强Ginberg博士的积极研究计划， 在加州大学旧金山分校广泛的基础设施，以支持她的目标，保持在神经退行性疾病的领导者， 特别是在神经病理学领域，并制定一个培训医学生的卓越计划， 学员和初级教师在POR有关年龄相关的神经病理学，也旨在缩小差距 由于神经病学家的神经病理学培训和神经退行性疾病培训中断， 神经病理学家

项目成果

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis.

后皮质萎缩的人口统计学、临床、生物标志物和神经病理学相关性：一项国际队列研究和个体参与者数据荟萃分析。

• DOI: 10.1016/s1474-4422(23)00414-3
• 发表时间: 2024
• 期刊: The Lancet. Neurology
• 作者: Chapleau,Marianne;LaJoie,Renaud;Yong,Keir;Agosta,Federica;Allen,IsabelElaine;Apostolova,Liana;Best,John;Boon,BaaylaDC;Crutch,Sebastian;Filippi,Massimo;Fumagalli,GiorgioGiulio;Galimberti,Daniela;Graff-Radford,Jonathan;Grinber
• 通讯作者: Grinber

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

• DOI: 10.1186/s40478-023-01681-z
• 发表时间: 2023-12-19
• 期刊: Acta neuropathologica communications
• 影响因子: 7.1

Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease.

• DOI: 10.3233/jad-180688
• 发表时间: 2018
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Ehrenberg AJ;Suemoto CK;França Resende EP;Petersen C;Leite REP;Rodriguez RD;Ferretti-Rebustini REL;You M;Oh J;Nitrini R;Pasqualucci CA;Jacob-Filho W;Kramer JH;Gatchel JR;Grinberg LT
• 通讯作者: Grinberg LT

Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study.

• DOI: 10.1007/s00702-021-02455-4
• 发表时间: 2022-01
• 期刊: JOURNAL OF NEURAL TRANSMISSION
• 影响因子: 3.3
• 作者: Nascimento, Camila;Nunes, Paula, V;Kim, Helena K.;Leite, Renata E. P.;Rodriguez, Roberta D.;De Oliveira, Katia Cristina;Brentani, Helena P.;Jacob-Filho, Wilson;Nitrini, Ricardo;Pasqualucci, Carlos A.;Grinberg, Lea T.;Suemoto, Claudia K.;Lafer, Beny
• 通讯作者: Lafer, Beny

Literacy, but not memory, is associated with hippocampal connectivity in illiterate adults.

识字（而非记忆）与文盲成年人的海马连接有关。

• DOI: 10.21203/rs.3.rs-3053775/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: dePaulaFrançaResende,Elisa;Lara,VivianP;Santiago,AnaLuisaC;Friedlaender,ClarisseV;Rosen,HowardJ;Brown,JesseA;Cobigo,Yann;Silva,LênioLG;deSouza,LeonardoCruz;Rincon,Luciana;Grinberg,LeaT;Maciel,FranciscaIP;Caramelli,
• 通讯作者: Caramelli,