Since the identification of TDP-43 in neuronal cytoplasmic inclusions (NCI) and dystrophic neurites (DN) in FTLD and neuronal intranuclear inclusions (NII), skein-like inclusions and glial inclusions in ALS, it has become apparent that abnormal TDP-43 localization and accumulation into amorphous aggregates and filamentous structures must be related to numerous pathological stressors [18], and this has been further exemplified by the identification of TDP-43 accumulation as a secondary pathology in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease cases [19], [20]. Here, TARDBP is linked to early-onset autosomal dominant Alzheimer disease.