About this Research Topic
FTLD, predominantly leading to degeneration of frontal cortical brain areas, is a genetically and neuropathologically complex group of syndromes, each showing distinct clinical features. For example, the behavioral variant frontotemporal dementia (bvFTD), the most common clinical subtype of FTLD, is primarily characterized by personality changes, whereas primary progressive aphasias (PPA) manifest as progressive loss of language functions. ALS, on the other hand, is characterized by degeneration of the upper and lower motor neurons, leading to muscle wasting and motor dysfunction. Some FTLD patients also show ALS-like motor symptoms and some ALS patients, in turn, exhibit cognitive impairment similarly to FTLD patients, suggesting that FTLD and ALS in fact form a disease spectrum with a subset of patients purely manifesting clinical symptoms of FTLD or ALS and with some showing overlapping clinical features of both disorders.
The idea of a disease spectrum is supported by the observations that FTLD and ALS may share an overlapping genetic background and show similar characteristic neuropathological alterations in the affected areas of the nervous system, suggesting common underlying disease mechanisms. Although a large number of patients suffer from a sporadic form of FTLD or ALS without a clear genetic disposition, several disease-causing mutations in both ALS and FTLD patients have been identified. These include e.g. mutations in the MAPT or GRN genes, typically causing FTLD, or in SOD1 causing ALS. More recently, genetic alterations that are associated with both FTLD and ALS in a large portion of patients with varying clinical symptoms, such as the hexanucleotide repeat expansion in C9orf72, have been found. However, it is unclear why the same genetic alteration can sometimes lead to FTLD and sometimes ALS.
The current genetic and mechanistic studies in humans and different disease models have started to increase our knowledge on the etiology of these diseases and their overlapping features. This knowledge will hopefully lead to the discovery of both predictive and diagnostic biomarkers and eventually effective therapies of these devastating diseases in the near future.
The goal of this Research Topic is to seek original or review article contributions that highlight novel insights into the genetics, clinical and pathological features, and underlying disease mechanisms of FTLD and/or ALS. This knowledge is expected to promote discovery of novel biomarkers or therapeutic strategies. Potential topics include but are not limited to the following:
- Genetics of FTLD and/or ALS
- Characteristics of patient clinical or neuropathological features associated with specific genetic backgrounds in FTLD and/or ALS
- Modeling pathological features of FTLD and/or ALS in different model systems
- Potential underlying molecular pathomechanisms associated with FTLD and/or ALS
- Insights into the contribution of of neuronal or glial cells in the pathogenesis of FTLD and/or ALS
Keywords: FTLD, ALS, genetics, neuropathology, clinical symptoms, disease models, pathogenic mechanisms
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