This is an application for a K24 award 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 (P50AG02350 and P01AG019724), and her collaborations with multidisciplinary researchers in the areas of dementia domestically and worldwide. To increase her mentoring skills, she proposes to participate in the UCSF Mentor Development Program. 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 role of recently described neurodegenerative changes in modifying the clinical phenotype of 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.

Public Health Relevance

Closing critical gaps in the understanding of AD etiopathogenesis by clarifying the neurobiological basis of heterogeneity in AD clinical presentation may result in novel biomarkers and targets for prevention and treatment of this devastating disease. This K24 research and training program will expand the capacity of a productive investigator to train advanced trainees in POR in age-related neuropathology. Furthermore, it will help her to make meaningful progress towards her long-term goal of conquering neurodegenerative diseases by carefully mapping disease-associate lesions in well-characterized human postmortem tissue and correlate these findings with clinical and genetics features.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Neuroscience of Aging Review Committee (NIA-N)
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Anderson, Dallas
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Suemoto, Claudia K; Grinberg, Lea T; Leite, Renata E P et al. (2018) Morphometric measurements of extracranial and intracranial atherosclerotic disease: A population-based autopsy study. Atherosclerosis 270:218-223
Nascimento, C; Di Lorenzo Alho, A T; Bazan Conceição Amaral, C et al. (2018) Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis. Neuropathol Appl Neurobiol 44:286-297
La Joie, Renaud; Ayakta, Nagehan; Seeley, William W et al. (2018) Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement :
Oh, Jun; Petersen, Cathrine; Walsh, Christine M et al. (2018) The role of co-neurotransmitters in sleep and wake regulation. Mol Psychiatry :
Theofilas, Panos; Ehrenberg, Alexander J; Nguy, Austin et al. (2018) Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans. Neurobiol Aging 61:1-12
Kim, Eun-Joo; Brown, Jesse A; Deng, Jersey et al. (2018) Mixed TDP-43 proteinopathy and tauopathy in frontotemporal lobar degeneration: nine case series. J Neurol 265:2960-2971
Suemoto, Claudia K; Ferretti-Rebustini, Renata E L; Rodriguez, Roberta D et al. (2017) Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study. PLoS Med 14:e1002267
Ehrenberg, A J; Nguy, A K; Theofilas, P et al. (2017) Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease. Neuropathol Appl Neurobiol 43:393-408
Fernández-Fournier, Mireya; Perry, David C; Tartaglia, Maria Carmela et al. (2017) Precipitous Deterioration of Motor Function, Cognition, and Behavior. JAMA Neurol 74:591-596
Dos Santos Matioli, Maria Niures Pimentel; Suemoto, Claudia Kimie; Rodriguez, Roberta Diehl et al. (2017) Diabetes is Not Associated with Alzheimer's Disease Neuropathology. J Alzheimers Dis 60:1035-1043

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