G-PDC, a neurodegenerative disease of Chamorro residents of Guam clinically characterized by either progressive cognitive impairment with extrapyramidal signs or motor neuron dysfunctions, is associated with cortical TDP-43-positive dystrophic neurites and neuronal and glial inclusions in gray and/or white matter, in addition to cortical neurofibrillary and glial tau pathology [204,205]. This evidence concerns the gene TARDBP and Cognitive impairment.