Introduction: The incidence of Frontotemporal Lobar Degeneration (FTLD)-related disorders and their characteristics are not well known. The "FRONTotemporal dementia Incidence European Research Study" (FRONTIERS) is designed to fill this gap.
Methods: FRONTIERS is a European prospective, observational population study based on multinational registries. FRONTIERS comprises 11 tertiary referral centers across Europe with long-lasting experience in FTLD-related disorders and comprehensive regional referral networks, enabling incidence estimation over well-defined geographical areas.
Endpoints: The primary endpoints are (1) the incidence of FTLD-related disorders across Europe; (2) geographic trends of FTLD-related disorders; (3) the distribution of FTLD phenotypes in different populations and ethnicities in Europe; (4) inheritance of FTLD-related disorders, including the frequencies of monogenic FTLD as compared to overall disease burden; and (5) implementation of data banking for clinical and biological material.
Expected Impacts: FRONTIERS will improve the understanding of FTLD-related disorders and their epidemiology, promoting appropriate public health service policies and treatment strategies.
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http://dx.doi.org/10.1002/alz.12414 | DOI Listing |
Brain Behav Immun
May 2024
Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy. Electronic address:
Autoantibodies directed against the GluA3 subunit (anti-GluA3 hIgGs) of AMPA receptors have been identified in 20%-25% of patients with frontotemporal lobar degeneration (FTLD). Data from patients and in vitro/ex vivo pre-clinical studies indicate that anti-GluA3 hIgGs negatively affect glutamatergic neurotransmission. However, whether and how the chronic presence of anti-GluA3 hIgGs triggers synaptic dysfunctions and the appearance of FTLD-related neuropathological and behavioural signature has not been clarified yet.
View Article and Find Full Text PDFInt J Mol Sci
December 2023
Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
The Transactivating response (TAR) element DNA-binding of 43 kDa (TDP-43) is mainly implicated in the regulation of gene expression, playing multiple roles in RNA metabolism. Pathologically, it is implicated in amyotrophic lateral sclerosis and in a class of neurodegenerative diseases broadly going under the name of frontotemporal lobar degeneration (FTLD). A common hallmark of most forms of such diseases is the presence of TDP-43 insoluble inclusions in the cell cytosol.
View Article and Find Full Text PDFActa Neuropathol Commun
March 2022
Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
TMEM106B, a type II lysosomal transmembrane protein, has recently been associated with brain aging, hypomyelinating leukodystrophy, frontotemporal lobar degeneration (FTLD) and several other brain disorders. TMEM106B is critical for proper lysosomal function and TMEM106B deficiency leads to myelination defects, FTLD related pathology, and motor coordination deficits in mice. However, the physiological and pathological functions of TMEM106B in the brain are still not well understood.
View Article and Find Full Text PDFGenome Med
March 2022
Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA.
Mol Psychiatry
March 2022
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
Frontotemporal lobar degeneration (FTLD) comprises a heterogenous group of fatal neurodegenerative diseases and, to date, no validated diagnostic or prognostic biomarkers or effective disease-modifying therapies exist for the different clinical or genetic subtypes of FTLD. Current treatment strategies rely on the off-label use of medications for symptomatic treatment. Changes in several neurotransmitter systems including the glutamatergic, GABAergic, dopaminergic, and serotonergic systems have been reported in FTLD spectrum disease patients.
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