The PPG titled Frontotemporal Dementia: Genes, Images and Emotions? has four Projects and five Cores. Project 3 probes socioemotional function to find optimal predictors using, multi-method laboratory and home assessments to separate frontotemporal dementia (FTD), Alzheimer's disease (AD), and mood disorders (MD), and to define brain regions that underlie emotion. Project 4 aims to improve diagnosis of behavioral variant FTD (bvFTD) versus AD, major depressive disorder (MDD), and bipolar disorder (BD) while studying the value of clinical, imaging, and other biomarker techniques to diagnose the different molecular causes for bvFTD. Project 6 uses novel models of network-based prediction grounded in task-free fMRI (tf-fMRI) to predict atrophy, the spread of atrophy, and progression of the tau PET signal in patients with suspected FTLD with tau, to elucidate disease mechanisms and refine methodology for research and treatment trials. Project 7 studies the language and non-language features of the 3 PPA subtypes svPPA, nfvPPA and logopenic variant PPA and will determine their longitudinal progression and improve their molecular diagnosis. Core A (Administrative and Clinical Core) evaluates PPG patients and collects clinical and biomarker measures. A new group with MDD and BD will be studied with the same measures used in FTD and AD. Core B (Neuropathology Core) will define FTLD, AD, and other pathology in our autopsied patients, while serving as a gold standard for diagnosis in all PPG projects. It will supply samples to basic scientists. Core C (Data Management and Biostatistics Core) will manage and facilitate visualization of PPG data and will offer biostatistical consultation across the cores. Core D (Genetics Core) will determine genetic mutations and risk genes in the PPG cohort and explore the role of whole exome and whole genome analyses and gene expression profiles to predict FTLD and AD subtypes. Core E (Imaging Core) will acquire and analyze MRI and PET images for research studies 3,4,6, and 7 and will use PET combined (amyloid [PIB] and tau [AV1451]) to detect and stage AD pathology and to explore the utility of AV1451 for detecting and tracking tau pathology in FTD.

Public Health Relevance

OVERALL NARRATIVE The FTD PPG will benefit public health through advancing knowledge of clinical diagnostic processes, genomic, basic, translational, and clinicopathological research regarding prevalent neurodegenerative diseases and common mood disorders of aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG019724-16
Application #
9280089
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7 (J1))
Program Officer
Hsiao, John
Project Start
2002-04-01
Project End
2022-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
16
Fiscal Year
2017
Total Cost
$1,967,009
Indirect Cost
$529,469
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Ossenkoppele, Rik; Rabinovici, Gil D; Smith, Ruben et al. (2018) Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA 320:1151-1162
Mandelli, Maria Luisa; Welch, Ariane E; Vilaplana, Eduard et al. (2018) Altered topology of the functional speech production network in non-fluent/agrammatic variant of PPA. Cortex 108:252-264
Pressman, Peter S; Shdo, Suzanne; Simpson, Michaela et al. (2018) Neuroanatomy of Shared Conversational Laughter in Neurodegenerative Disease. Front Neurol 9:464
Caverzasi, Eduardo; Mandelli, Maria Luisa; Hoeft, Fumiko et al. (2018) Abnormal age-related cortical folding and neurite morphology in children with developmental dyslexia. Neuroimage Clin 18:814-821
Toller, Gianina; Brown, Jesse; Sollberger, Marc et al. (2018) Individual differences in socioemotional sensitivity are an index of salience network function. Cortex 103:211-223
Caplan, Alyssa; Marx, Gabe; Elofson, Jonathan et al. (2018) A case of semantic variant primary progressive aphasia with Pick's pathology. Neurocase 24:90-94
Watson, Christa L; Possin, Katherine; Allen, I Elaine et al. (2018) Visuospatial Functioning in the Primary Progressive Aphasias. J Int Neuropsychol Soc 24:259-268
Brown, Casey L; Lwi, Sandy J; Goodkind, Madeleine S et al. (2018) Empathic Accuracy Deficits in Patients with Neurodegenerative Disease: Association with Caregiver Depression. Am J Geriatr Psychiatry 26:484-493
Geier, Ethan G; Bourdenx, Mathieu; Storm, Nadia J et al. (2018) Rare variants in the neuronal ceroid lipofuscinosis gene MFSD8 are candidate risk factors for frontotemporal dementia. Acta Neuropathol :
Sturm, Virginia E; Brown, Jesse A; Hua, Alice Y et al. (2018) Network Architecture Underlying Basal Autonomic Outflow: Evidence from Frontotemporal Dementia. J Neurosci 38:8943-8955

Showing the most recent 10 out of 607 publications