This is an application for a K-23 Mentored Career Development Award entitled """"""""Amyloid PET in AD, FTLD &PPA: Diagnosis, Functional &Structural Correlations."""""""" The primary goal of the proposed research is to apply PET imaging with the amyloid-beta (AP) ligand Pittsburgh Compound-B (PIB) towards the differential diagnosis of dementia, while simultaneously studying the relationships between amyloid deposition, clinical presentation, and brain structure and function. Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are two leading causes of dementia with distinct histopathologies. Primary progressive aphasia (PPA) is a clinical syndrome that can be caused by FTLD or (less commonly) AD pathology. PIB is a novel PET tracer that specifically binds Ap amyloid, a pathologic hallmark of AD that is not part of the FTLD spectrum.
The specific aims of this study are: (1) To measure the utility of PIB-PET in distinguishing AD and FTLD;(2) To identify clinical features that predict the presence of Ap amyloid in PPA and FTLD, and thereby refine diagnostic criteria;(3) To study the relationships between clinical presentation, regional Ap amyloid deposition and neuronal functional and structural integrity using PIB-PET, FDG-PET, and MRI-based cortical thickness measurements. Overall, the proposal seeks to establish PIB-PET as an important clinical tool for improving diagnostic accuracy in dementia, and an important scientific tool for studying the role of Ap amyloid in the pathogenesis of AD. The applicant's long-term goal is to become an independent translational investigator in dementia with expertise in structural, functional and molecular neuroimaging. The applicant seeks training in: (1) neuroimaging, (2) neuropathology and neurobiology of -disease, (S)-biomarker analysis,. (4.) .biostatistics and. data analysis, (5) cognitive and systems neuroscience, (6) clinical dementia care, (7) presentation, Dublication and grant writing and (8) responsible conduct of research. The training program includes mplementing the proposed research plan, didactic courses and instruction from mentors and consultants. Dementia is a leading cause of age-related morbidity and mortality, and a growing strain on health-care resources. The proposed research studies the potential of a new brain imaging technique to improve diagnostic accuracy in dementia, and to study the biology of Alzheimer's disease.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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National Institute on Aging Initial Review Group (NIA)
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Hsiao, John
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University of California San Francisco
Schools of Medicine
San Francisco
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Tarawneh, Rawan; D'Angelo, Gina; Crimmins, Dan et al. (2016) Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease. JAMA Neurol 73:561-71
Voyle, N; Kim, M; Proitsi, P et al. (2016) Blood metabolite markers of neocortical amyloid-? burden: discovery and enrichment using candidate proteins. Transl Psychiatry 6:e719
Villeneuve, Sylvia; Rabinovici, Gil D; Cohn-Sheehy, Brendan I et al. (2015) Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation. Brain 138:2020-33
Ashton, Nicholas J; Kiddle, Steven J; Graf, John et al. (2015) Blood protein predictors of brain amyloid for enrichment in clinical trials? Alzheimers Dement (Amst) 1:48-60
Chan, Lung Tat Andrew; Lynch, Whitney; De May, Mary et al. (2015) Prodromal posterior cortical atrophy: clinical, neuropsychological, and radiological correlation. Neurocase 21:44-55
Wagshal, Dana; Sankaranarayanan, Sethu; Guss, Valerie et al. (2015) Divergent CSF ? alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 86:244-50
Migliaccio, Raffaella; Agosta, Federica; Possin, Katherine L et al. (2015) Mapping the Progression of Atrophy in Early- and Late-Onset Alzheimer's Disease. J Alzheimers Dis 46:351-64
Sánchez-Juan, Pascual; Ghosh, Pia M; Hagen, Jayne et al. (2014) Practical utility of amyloid and FDG-PET in an academic dementia center. Neurology 82:230-8
Lehmann, Manja; Ghosh, Pia M; Madison, Cindee et al. (2014) Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients. J Neurol Neurosurg Psychiatry 85:266-73
Perry, David C; Lehmann, Manja; Yokoyama, Jennifer S et al. (2013) Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 70:774-8

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