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All cases were from the Mayo Clinic brain bank for neurodegenerative disorders and most were followed longitudinally in the ALS Clinic. Cases with moderate\u2010to\u2010severe Alzheimer's disease neuropathological change were excluded. The 55 cases included in the study were divided into three groups by age at death: 75\u2009years or older (old\u2010ALS, <jats:italic>n<\/jats:italic>\u00a0=\u00a08), 64\u201374\u2009years (middle\u2010ALS, <jats:italic>n<\/jats:italic>\u00a0=\u00a023), and 63\u2009years or younger (young\u2010ALS, <jats:italic>n<\/jats:italic>\u00a0=\u00a024). Clinical features, including disease duration, initial symptoms, and ALS Cognitive Behavior Score (ALS\u2010CBS), were summarized. Sections of paraffin\u2010embedded tissue from the motor cortex, basal forebrain, medial temporal lobe, and middle frontal gyrus were processed for phospho\u2010TDP\u201043 immunohistochemistry. The burden of TDP\u201043 pathology was analyzed using digital image analysis. The TDP\u201043 burden in the limbic system (i.e., amygdala, dentate gyrus and CA1 sector of the hippocampus, subiculum, and entorhinal cortex) was greater in old\u2010ALS than in young\u2010ALS and middle\u2010ALS. TDP\u201043 burden in the middle frontal gyrus was sparse and did not differ between the three groups. The average of ALS\u2010CBS was not different between the three groups. The present study shows that the amygdala and hippocampus are vulnerable to TDP\u201043 pathology in older patients with ALS. We discuss the evidence for and against this pathology being related to concurrent limbic\u2010predominant, age\u2010related TDP\u201043 encephalopathy neuropathologic change.<\/jats:p>","DOI":"10.1111\/bpa.13100","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T05:29:05Z","timestamp":1655530145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Old age amyotrophic lateral sclerosis and limbic TDP\u201043 pathology"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4088-5005","authenticated-orcid":false,"given":"Aya","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida 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