Biomarkers in frontotemporal lobar degeneration

Abstract

Recent findings assessing the utility of neuroimaging and biofluid biomarkers are reviewed that help identify patients with frontotemporal lobar degeneration (FTLD) spectrum abnormality. Neuroimaging studies using T1 structural MRI and diffusion tensor imaging (DTI) distinguish between patients with FTLD and Alzheimer's disease, although the reliability of these group-level findings in individual patients has been assessed only rarely. However, innovative analyses such as support vector machine approaches are able to integrate T1 and DTI imaging results and to identify specific MRI profiles that distinguish between individual patients with FTLD and Alzheimer's disease. Novel radioligand positron emission tomography assessments also can recognize Alzheimer's disease patients with a clinical phenotype resembling that seen in FTLD. Biofluid studies identify about 15% of patients with FTLD due to a genetic mutation that is associated with the specific histopathologic features of TDP-43 or a tauopathy. Other genetically-based risk factors and targeted proteomic searches of plasma and cerebrospinal fluid have suggested additional markers in sporadic cases of FTLD that will lead to the identification of patients with TDP-43 or tau histopathology. Great progress has been made in developing biomarkers for FTLD, but additional work is needed to extend these advances so that the histopathologic abnormality causing FTLD can be specified in an individual patient.