Neuroimaging in frontotemporal lobar degeneration - Predicting molecular pathology

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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.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalNature Reviews Neurology
Volume8
Issue number3
DOIs
StatePublished - Mar 2012

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Frontotemporal Lobar Degeneration
Molecular Pathology
Neuroimaging
Atrophy
Proteins
Biomarkers
Pathology
Frontotemporal Dementia
Clinical Pathology
Gliosis
Microtubule-Associated Proteins
DNA-Binding Proteins
Frontal Lobe
Temporal Lobe
Sarcoma
Phenotype

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

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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.",
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