Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). There are currently no effective FTLD therapies, although new drugs are reaching the stage where clinical trials are warranted. The overarching goal of this proposal is to build a FTLD clinical research consortium (FTLD CRC) to support the development of FTLD therapies. The FTLD CRC will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Patients will be evaluated at 13 clinical sites throughout North America, and a genetics core will genotype all individuals for FTLD associated genes. Clinical research projects will focus on specific FTLD syndromes where there is a strong correlation between clinical syndrome and underlying pathology, who are targeted for enrollment in new trials. Research Project 1 will collect cross-sectional data in sporadic FTLD patients using a new FTLD assessment battery, as well as screening all individuals for known FTLD-causing mutations and evidence of systemic inflammation, to prepare for trials of anti-tau and anti-inflammatory agents. Research Project 2 will collect longitudinal clinical and MRl data on familial FTLD (f-FTLD) individuals who carry mutations in MAPT, GRN and C90RF72 and their asymptomatic family members to enable disease prevention clinical trials.
Our specific aims are to: 1) build a FTLD clinical trials network to facilitate the design and conduct of clinical trials;2) determine the clinical, genetic and systemic inflammatory cytokine profile of sporadic FTLD targeted for new trials: semantic variant PPA, FTD with amyotrophic lateral sclerosis and PSPS;3) determine the natural history of asymptomatic and symptomatic f-FTLD patients using novel clinical measures and MR imaging over one year;4) obtain pilot data using the new tau PET imaging agent PBB3 in FTLD, and other novel FTLD biomarkers and clinical tools that may be employed in future trials;5) train clinical researchers focused on FTLD therapeutic development.

Public Health Relevance

Frontotemporal Lobar Degeneration (FTLD) is a group of rare, fatal brain diseases that cause thinking and movement problems and for which there are currently no effective therapies. This project will build a North American clinical research network to prepare for studies of new FTLD treatments. Developing FTLD therapies may also help to find a cure for more common disorders such as Alzheimer's disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Sutherland, Margaret L
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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La Joie, Renaud; Bejanin, Alexandre; Fagan, Anne M et al. (2018) Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample. Neurology 90:e282-e290
Iaccarino, Leonardo; Tammewar, Gautam; Ayakta, Nagehan et al. (2018) Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease. Neuroimage Clin 17:452-464
Henry, Maya L; Hubbard, H Isabel; Grasso, Stephanie M et al. (2018) Retraining speech production and fluency in non-fluent/agrammatic primary progressive aphasia. Brain 141:1799-1814
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
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
Deutschländer, Angela B; Boeve, Bradley F; Rosen, Howard J et al. (2018) Tau Mutations as a Novel Risk Factor for Cancer-Letter. Cancer Res 78:6523-6524
Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C et al. (2018) Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration. Neurology 90:e1047-e1056
Santos-Santos, Miguel A; Rabinovici, Gil D; Iaccarino, Leonardo et al. (2018) Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia. JAMA Neurol 75:342-352
Bergeron, David; Gorno-Tempini, Maria L; Rabinovici, Gil D et al. (2018) Prevalence of amyloid-? pathology in distinct variants of primary progressive aphasia. Ann Neurol 84:729-740

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