Abstract
Frontotemporal lobar degeneration (FTLD) encompasses a group of diseases characterized by neuronal loss and gliosis of the frontal and temporal lobes. Almost all cases of FTLD can be classified into three categories on the basis of deposition of one of three abnormal proteins: the microtubule-associated protein tau, TAR DNA-binding protein 43, or fused in sarcoma. The specific diagnoses within each of these three categories are further differentiated by the distribution and morphological appearance of the protein-containing inclusions. Future treatments are likely to target these abnormal proteins; the clinical challenge, therefore, is to be able to predict molecular pathology during life. Clinical diagnosis alone has had variable success in helping to predict pathology, and is particularly poor in the diagnosis of behavioral variant frontotemporal dementia, which can be associated with all three abnormal proteins. Consequently, other biomarkers of disease are needed. This Review highlights how patterns of atrophy assessed on MRI demonstrate neuroanatomical signatures of the individual FTLD pathologies, independent of clinical phenotype. The roles of these patterns of atrophy as biomarkers of disease, and their potential to help predict pathology during life in patients with FTLD, are also discussed.
Key Points
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The term frontotemporal lobar degeneration (FTLD) encompasses a group of pathological disorders that can be characterized by deposition of abnormal forms of tau, TAR DNA-binding protein 43 or fused in sarcoma
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Predicting the underlying pathology in patients with FTLD will be particularly important when treatments become available that target these abnormal proteins
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Neuroimaging studies in patients with autopsy-confirmed FTLD have shown that the different pathological diagnoses have specific neuroanatomical signatures
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The imaging signatures of pathology in patients with FTLD disorders may be useful for predicting the underlying pathology in these individuals
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Acknowledgements
K. A. Josephs and J. L. Whitwell are funded by NIH grants R01-DC010367, R01-AG037491 and R21-AG38736, and The Dana Foundation.
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J. L. Whitwell researched data for the article, provided substantial contribution to discussions of the content and wrote the article. K. A. Josephs provided substantial contribution to discussion of the content and reviewed and edited the article before submission.
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Supplementary Table 1
Summary of regional imaging findings from group studies that assessed patterns of atrophy in pathologically or genetically confirmed FTLD-tau diseases (DOC 79 kb)
Supplementary Table 2
Summary of regional imaging findings from group studies that assessed patterns of atrophy in pathologically or genetically confirmed FTLD-TDP or FTLD-FUS diseases (DOC 76 kb)
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Whitwell, J., Josephs, K. Neuroimaging in frontotemporal lobar degeneration—predicting molecular pathology. Nat Rev Neurol 8, 131–142 (2012). https://doi.org/10.1038/nrneurol.2012.7
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DOI: https://doi.org/10.1038/nrneurol.2012.7
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