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Principal Investigator: MARIA LUISA GORNO TEMPINI
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $5,446,505
Funding agency: National Institute on Aging
PROJECT SUMMARY—Frontotemporal Dementia (FTD): Genes, Images, and Emotions
Frontotemporal dementia (FTD) research is entering a new era of therapeutic discovery, spurred in part by
contributions from this program project grant (PPG), entitled “Frontotemporal Dementia: Genes, Images, and
Emotions,” which has a 20-year history of productivity and collaboration. In renewal, this PPG has been designed
to close important clinical-translational knowledge gaps that could, if unaddressed, impede progress toward new
therapies. The PPG will include four projects and seven cores. Project 1 will dissect the cognitive and emotional
processes disrupted in FTD using novel laboratory and neuroimaging approaches and will translate this
knowledge into automated, scalable tools for pathology prediction and disease-monitoring. Project 2 will link
transcriptomic and proteomic discovery platforms to TDP-43 loss-of-function biology, seeking to develop new
plasma-based molecular diagnostic and disease monitoring biomarkers. Project 3 will use laboratory-based
emotions research methods to evaluate FTD caregivers, a group at risk for poor health outcomes, with an eye
toward enhanced caregiver wellbeing and patient clinical trial participation. Project 4 will seek to identify sources
of heterogeneity in FTD clinical progression and treatment goals. Core A (Administration) will oversee all aspects
of the PPG to assure success of the project. Core B (Clinical) will recruit and evaluate patients and caregivers,
including those from groups historically underrepresented in research, and collect clinical, neuropsychological,
and functional assessments. Core C (Data Management and Biostatistics) will ensure data quality and availability
and provide biostatistical consultation to all projects. Core D (Neuropathology) will coordinate autopsies and
render neuropathological diagnoses, serving as the diagnostic gold standard and providing tissue for basic
science and biomarker discovery efforts. Core E (Imaging) will acquire and process MRI scans and obtain
amyloid-PET to detect AD in selected diagnostically uncertain patients. Core F (Genetics) will identify known
genetic FTD pathogenic and risk variants through whole-exome sequencing and provide gene expression
profiling in support of Project 2. Core G (Biospecimens) will obtain and bank biofluid specimens, provide samples
and proteomics data to Projects 2 and 4, and use established fluid biomarkers to detect neurodegeneration and
AD pathophysiology. These tightly integrated projects and cores will support our overall aim of accelerating
progress in the era of FTD therapeutic discovery.
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Serum><Population><Populations at Risk><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Primary Progressive Aphasia><Primary Senile Degenerative Dementia><Process><Productivity><Program Project Grant><Program Research Project Grants><Proteomics><Public Health><Rad.-PET><Recording of previous events><Research><Research Methodology><Research Methods><Research Program Projects><Research Specimen><Reticuloendothelial System, Serum, Plasma><Risk-associated variant><Sample Size><Sampling><Sorting><Source><Specimen><Syndrome><System><TAR DNA-binding protein 43><TDP-43><TDP43><Technology><Therapeutic><Tissues><Transcript Expression Analyses><Transcript Expression Analysis><Translating><Translational Research><Translational Science><United States National Institutes of Health><Variant><Variation><aging associated disease><aging related disease><analyze gene expression><behavioral variant FTD><behavioral variant frontotemporal degeneration><behavioral variant frontotemporal dementia><bio-markers><biologic marker><biomarker><biomarker discovery><biomarker validation><bvFTD><care giver well-being><care giver wellbeing><caregiver interventions><caregiver wellbeing><caregivers for persons living with dementia><caregivers for persons with dementia><caregivers of individuals with dementia><caregivers of patients with dementia><clinical heterogeneity><clinical translation><clinical trial enrollment><clinically translatable><cognitive process><consultation><data access><data management><data quality><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><dementia care giver><design><designing><disease of aging><disorder of aging><exome sequencing><exome-seq><fMRI scan><faces><facial><fluid><front temporal dementia><frontal lobe dementia><frontotemporal lobar dementia><frontotemporal lobe degeneration associated with dementia><functional MRI scan><functional magnetic resonance imaging 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outcome><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><postmortem><primary degenerative dementia><prognostication><protein TDP-43><protein TDP43><recruit><reduced health outcome><research and methods><resilience factor><resiliency factor><risk allele><risk gene><risk genotype><risk loci><risk locus><risk variant><senile dementia of the Alzheimer type><social><success><tau><tau Proteins><tau factor><tool><transcriptional profiling><transcriptomics><translation research><translational investigation><worse health outcome><τ Proteins>