Horizon in Frontotemporal Lobar Degeneration Related Disorder

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About this Research Topic

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Background

Frontotemporal lobar degeneration (FTLD) encompasses a spectrum of focal neurodegenerative disorders with progressive atrophy of the frontal and temporal lobes. FTLD-related disorders are heterogeneous clinical conditions characterized by social dysfunction and personality changes as well as impairments in language, executive and motor functions. Current clinical diagnostic criteria characterize specific manifestations of FTLD, including transtemporal behavioral dementia (bvFTD), primary progressive aphasia with agrammatic variant (avPPA) and semantic variant (svPPA) subtypes, and movement disorders, including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and FTD with amyotrophic lateral sclerosis (FTD-ALS).

FTLD is a genetically heterogeneous neurodegenerative disorder. In up to 40% of patients with FTLD, there is a family history of the disease. Genetics may indicate, at least in part, different underlying disease mechanisms. Many cases of familial FTLD have been linked to gene, including the microtubule-associated protein tau (MAPT), progranulin (GRN), C9orf72, valosin-containing protein (VCP), and charged multivesicular body protein 2B (CHMP2B) genes; others may be the result of alterations in as yet undiscovered genes. Although much progress has been made in the field of genetics of FTLD, most genetic causes remain unknown.

Neuropsychological features may help in the early detection and differentiation of the various subtypes. Exploration of sensitive and specific neuropsychological testing strategies in both preclinical and clinical settings should enable a more standardized, automated, and consistent approach to screening and assessment of FTLD. In addition, biomarkers based on neuro-molecular imaging provide reliable support for clinical diagnosis by visualizing and quantifying pathological changes in vivo. Despite all these promising advances, accurate and early diagnosis of FTLD-related diseases is becoming increasingly difficult due to the atypical and overlapping clinical manifestations within the broad spectrum of FTLD. Moreover, the underlying mechanism of pathogenicity has not been fully elucidated.

This Research Topic aims to highlight the growing role and importance of genetic, neuropsychological and neuro/molecular imaging tools in clinical practice for FTLD-related disorders in general. We intend to 1) gather evidence for the feasibility of a comprehensive diagnostic framework that includes genetic, neuropsychological, structural, functional, and molecular imaging tools, 2) identify sensitive and specific diagnostic imaging biomarkers in both preclinical and clinical settings, and 3) additionally explore the mechanisms underlying clinical manifestations. We focus on the potential role of genetics, neuropsychology, various imaging modalities including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and functional MRI (fMRI), and positron emission tomography (PET) with advanced radiotracers, targeting amyloid, tau, dopamine transporters and synapse pathology to identify disease-related sensitive predictive markers, enable early and accurate FTLD diagnosis and investigate underlying pathogenesis mechanisms.

We welcome submissions of Original Research, Case Reports, reviews, Mini-Reviews, Perspectives, Systematic Reviews, and Meta-Analyses, including but not limited to the following topics related to FTLD-related disorders:
- Genetics
- Neuropsychological research
- Structural imaging
- Diffusion Tensor imaging
- Functional imaging
- Molecular Imaging
- Diversity and inclusivity in FTD spectrum disorders

Keywords: Frontotemporal Lobar Degeneration, Genetics, Neuropsychology, Biomarkers, Diffusion Tensor Imaging, Positron Emission Tomography, Functional Magnetic Resonance Imaging, Magnetic Resonance Imaging

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