Frontotemporal Lobar degenerafion (FTLD) manifests clinically with progressive behavioral and/or language deficits. Subtypes of FTLD are classified neuropathologically by the protein composition of cellular inclusion bodies. The most common neuropathological correlates of FTLD have TAR DNA binding protein (TDP-43) inclusions (FTLD-TDP) or tau inclusions (FTLD-tau). FTLD is frequenfiy familial and can occur as an autosomal dominantly inherited disorder. Genes with mutations causing FTLD include /W/APT (encodes tau) and GRN (encodes progranulin) among others, each of which is associated with a specific FTLD pathological subtype: GRN mutations with FTLD-TDP and MAPT mutafions with FTLD-tau. Studying the genetics of FTLD can help elucidate its etiology and pathophysiology and provide targets for therapy as well as identify risk factors that modify disease risk or phenotype. To enable genefic studies of FTLD the Genetics Core, as an integral part of this Program Project Grant, will collect and bank DNA from Clinical Core B subjects with FTLD and autopsy brains characterized in the Neuropathology Core as well as control samples. For participafing individuals, a study coordinator trained as a certified genetic counselor will provide genetic educafion to foster a better understanding of the research and to obtain informed consent. Banked DNA will be used for genetic analysis by the Core itself, as well as by Project 1, and other collaborators within and outside of UPenn. Genetic analysis of FTLD associated genes willbe performed by the Core and in collaboration with Project 1. Genotype data will enable clinical, pathologic and genetic correlafions with data from Projects 1 and 3 and the Clinical and Neuropathology Cores with stafisfical analysis by the Biostatistics and Data Management Core. Projects 2 and 4 will use genotype data for case selection for analysis. Finally, the Genefics Core will coordinate with the Hosp. of the Univ. of Penn Molecular Pathology Lab to make CLIA-certified genetic testing available. To this end, the Core will identify new genetic tests which are ready for translafion into clinical tests and assist with validation by providing primer sequences, protocols, and samples.
The Studies proposed in this Core taken together with the complementary activities in the other Cores and Projects in this PPG will lead to improved understanding of the genetics of FTLD and related neurodegenerative disorders and will contrilDute samples to collaborafive projects advancing the field as a whole.
|Berson, Amit; Sartoris, Ashley; Nativio, Raffaella et al. (2017) TDP-43 Promotes Neurodegeneration by Impairing Chromatin Remodeling. Curr Biol 27:3579-3590.e6|
|Spinelli, Edoardo G; Mandelli, Maria Luisa; Miller, Zachary A et al. (2017) Typical and atypical pathology in primary progressive aphasia variants. Ann Neurol 81:430-443|
|Cousins, Katheryn A Q; Ash, Sharon; Irwin, David J et al. (2017) Dissociable substrates underlie the production of abstract and concrete nouns. Brain Lang 165:45-54|
|Nevler, Naomi; Ash, Sharon; Jester, Charles et al. (2017) Automatic measurement of prosody in behavioral variant FTD. Neurology 89:650-656|
|Phillips, Jeffrey S; Da Re, Fulvio; Dratch, Laynie et al. (2017) Neocortical origin and progression of gray matter atrophy in nonamnestic Alzheimer's disease. Neurobiol Aging 63:75-87|
|Zylstra, Bradley; Netscher, George; Jacquemot, Julien et al. (2017) Extended, continuous measures of functional status in community dwelling persons with Alzheimer's and related dementia: Infrastructure, performance, tradeoffs, preliminary data, and promise. J Neurosci Methods :|
|Lee, Edward B; Porta, Sílvia; Michael Baer, G et al. (2017) Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration. Acta Neuropathol 134:65-78|
|Dong, Aoyan; Toledo, Jon B; Honnorat, Nicolas et al. (2017) Heterogeneity of neuroanatomical patterns in prodromal Alzheimer's disease: links to cognition, progression and biomarkers. Brain 140:735-747|
|Kim, Benjamin J; Irwin, David J; Song, Delu et al. (2017) Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration. Neurology 89:1604-1611|
|Ballatore, Carlo; Brunden, Kurt R; Trojanowski, John Q et al. (2017) Non-Naturally Occurring Small Molecule Microtubule-Stabilizing Agents: A Potential Tactic for CNS-Directed Therapies. ACS Chem Neurosci 8:5-7|
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