TDP-43 neuropathology is strongly associated with late-life cognitive decline67 in adults >80 years of age and is recognized as a unique disease entity named limbic-predominant age-related TDP-43 encephalopathy (LATE).68 LATE neuropathological change (LATE-NC) is associated with amnestic cognitive impairment mimicking Alzheimer’s disease (AD)68 and co-occurs with hippocampal sclerosis in ~40% of cases,69 AD neuropathology in 25%−37% of cases,70,71 or other mixed pathologies (e.g., Lewy body disease), and more rarely in isolation (~6%). The gene discussed is TARDBP; the disease is Alzheimer disease.