Project 6, entitled """"""""Network biomarkers"""""""" will develop novel network connectivity analyses for detecting and monitoring preclinical FTD and early clinical bvFTD. The overarching goal is to move beyond prevaling barriers to implementing intrinsic connectivity network (ICN) mapping as a neurodegenerative disease biomarker. Recent research suggests that each neurodegenerative syndrome targets a specific, large-scale distributed network that can be identified in the healthy brain using ICN methods. As a non-invasive, repeatable, dynamic functional imaging modality, ICN mapping has the potential to play a vital role in FTD drug discovery. How ICNs break down in presymptomatic FTD gene mutation carriers and patients with early bvFTD, however, remains unknown. Furthermore, no data are available regarding longitudinal ICN changes in FTD or how ICN integrity relates to clinical deficits. Existing barriers to addressing these questions and developing ICN biomarkers include lack of reliability data in patients and the need to build methodological consensus. In Project 6, we will seek to overcome these issues and address key questions about early sites, longitudinal progression, and symptom-relevance of ICN changes by studying subjects with preclinical FTD (asymptomatic FTD gene mutation carriers), early clinical bvFTD, early svPPA, and healthy controls recruited through Core A (Clinical), genotyped through Core D (Genetics), imaged through Core E (Imaging) and characterized in terms of emotion processing in Project 3 (Emotions). We will pursue the following specific aims: (1) To determine the most reliable and sensitive ICN analysis strategy for detecting preclinical FTD and early clinical bvFTD at first evaluation, (2) To identify longitudinal network connectivity changes in preclinical FTD and early clinical bvFTD over 6- and 12-month intervals, and (3) To link specific ICN changes to loss of emotional functioning in preclinical FTD, early bvFTD and svPPA (with Project 3). Successful completion of the proposed studies could help provide the field with a non-invasive diagnostic and disease monitoring neuroimaging biomarker for early FTD and, potentially, for related neurodegenerative diseases.
Project 6 will benefit the public health by developing a biomarker for neurodegenerative disease research. If successful, this work could accelerate the search for new therapies for prevalent age-related neurodegnerative diseases.
| Miller, Zachary A; Rosenberg, Lynne; Santos-Santos, Miguel A et al. (2018) Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy. JAMA Neurol 75:728-737 |
| Rojas, Julio C; Stephens, Melanie L; Rabinovici, Gil D et al. (2018) Multiproteinopathy, neurodegeneration and old age: a case study. Neurocase 24:1-6 |
| Dijkstra, Anke A; Lin, Li-Chun; Nana, Alissa L et al. (2018) Von Economo Neurons and Fork Cells: A Neurochemical Signature Linked to Monoaminergic Function. Cereb Cortex 28:131-144 |
| Mok, Sue-Ann; Condello, Carlo; Freilich, Rebecca et al. (2018) Mapping interactions with the chaperone network reveals factors that protect against tau aggregation. Nat Struct Mol Biol 25:384-393 |
| Erkkinen, Michael G; Zúñiga, Raquel Gutiérrez; Pardo, Cristóbal Carnero et al. (2018) Artistic Renaissance in Frontotemporal Dementia. JAMA 319:1304-1306 |
| Schneider, Raphael; McKeever, Paul; Kim, TaeHyung et al. (2018) Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study. J Neurol Neurosurg Psychiatry 89:851-858 |
| Ljubenkov, Peter A; Staffaroni, Adam M; Rojas, Julio C et al. (2018) Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory. Ann Clin Transl Neurol 5:1250-1263 |
| 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 |
| Kim, Eun-Joo; Brown, Jesse A; Deng, Jersey et al. (2018) Mixed TDP-43 proteinopathy and tauopathy in frontotemporal lobar degeneration: nine case series. J Neurol 265:2960-2971 |
| 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 |
Showing the most recent 10 out of 607 publications
