Imaging Biomarkers for Neurodegeneration in Presymptomatic Familial Frontotemporal Lobar Degeneration

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by behavioral changes, language abnormality, as well as executive function deficits and motor impairment. In about 30–50% of FTLD patients, an autosomal dominant pattern of inheritance was found with major mutations in the MAPT, GRN, and the C9orf72 repeat expansion. These mutations could lead to neurodegenerative pathology years before clinical symptoms onset. With potential disease-modifying treatments that are under development, non-invasive biomarkers that help determine the early brain changes in presymptomatic FTLD patients will be critical for tracking disease progression and enrolling the right participants into the clinical trials at the right time during the disease course. In recent years, there is increasing evidence that a number of imaging biomarkers show the abnormalities during the presymptomatic stage. Imaging biomarkers of presymptomatic familial FTLD may provide insight into the underlying neurodegenerative process years before symptom onset. Structural magnetic resonance imaging (MRI) has demonstrated cortical degeneration with a mutation-specific neurodegeneration pattern years before onset of clinical symptoms in presymptomatic familial FTLD mutation carriers. In addition, diffusion tensor imaging (DTI) has shown the loss of white matter microstructural integrity in the presymptomatic stage of familial FTLD. Furthermore, proton magnetic resonance spectroscopy (1H MRS...

Source: Frontiers in Neurology - February 27, 2020 Category: Neurology Source Type: research