Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD) is a group of heterogeneous sporadic and familial neurodegenerative disorders. They are the second most common cause of dementia after Alzheimer's disease (AD) in patients <65 and ~50% of FTLD patients develop abundant tau pathologies in neurons and glia (FTLD-Tau). Exciting new data from Project 2 and provocative recent reports provide models to test novel hypothesis concerning mechanisms of tauopathies. The first hypothesis we test is based on our recent observations that introduction of small amounts of exogenous tau fibril "seeds" into tau overexpressing cells recruits endogenous tau to fibrillize into abundant tau filamentous structures seeded by the exogenously introduced tau fibrils. These results suggest a "seeding" mechanism of tau tangle pathogenesis whereby fibrillar tau "seeds" serve as a "nidus" for recruiting soluble tau into fibrillar aggregates that enlarge as a result. The second hypothesis we test is based on recent data that tau fibrils spread from cell-to-cell in vitro and in tau transgenic (Tg) mouse models consistent with the notion of a prion-like mechanism for the propagation and spreading of tau pathology and disease progression. Successful completion of the studies to test these hypotheses here will address fundamental disease mechanisms of FTLD-Tau, which, in conjunction with research advances from other projects in this PPG will accelerate efforts to find better therapeutic interventions for patients with diverse FTLDs.
Project 2 will provide in depth understanding on the fundamental disease mechanisms for tauopathies in general and FTLD-Tau in particular. This knowledge, together with the model systems developed in Project 2 will accelerate efforts to develop more effective therapies for the treatment of patients with FTLD-Tau and other tauopathies such as AD.
|Price, Amy Rose; Peelle, Jonathan E; Bonner, Michael F et al. (2016) Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as Revealed by High-Definition Transcranial Direct Current Stimulation. J Neurosci 36:3829-38|
|Makani, Vishruti; Zhang, Bin; Han, Heeoon et al. (2016) Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy. Acta Neuropathol Commun 4:106|
|Ash, Sharon; Ternes, Kylie; Bisbing, Teagan et al. (2016) Dissociation of quantifiers and object nouns in speech in focal neurodegenerative disease. Neuropsychologia 89:141-52|
|Santos-Santos, Miguel A; Mandelli, Maria Luisa; Binney, Richard J et al. (2016) Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration. JAMA Neurol 73:733-42|
|Cousins, Katheryn A Q; Ash, Sharon; Irwin, David J et al. (2016) Dissociable substrates underlie the production of abstract and concrete nouns. Brain Lang 165:45-54|
|Kovalevich, Jane; Cornec, Anne-Sophie; Yao, Yuemang et al. (2016) Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer's Disease and Related Tauopathies. J Pharmacol Exp Ther 357:432-50|
|Vu, An T; Phillips, Jeffrey S; Kay, Kendrick et al. (2016) Using precise word timing information improves decoding accuracy in a multiband-accelerated multimodal reading experiment. Cogn Neuropsychol 33:265-75|
|Shinagawa, Shunichiro; Catindig, Joseree Ann; Block, Nikolas R et al. (2016) When a Little Knowledge Can Be Dangerous: False-Positive Diagnosis of Behavioral Variant Frontotemporal Dementia among Community Clinicians. Dement Geriatr Cogn Disord 41:99-108|
|Spiller, Krista J; Restrepo, Clark R; Khan, Tahiyana et al. (2016) Progression of motor neuron disease is accelerated and the ability to recover is compromised with advanced age in rNLS8 mice. Acta Neuropathol Commun 4:105|
|McMillan, Corey T; Irwin, David J; Nasrallah, Ilya et al. (2016) Multimodal evaluation demonstrates in vivo (18)F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:935-937|
Showing the most recent 10 out of 487 publications