{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:15:50Z","timestamp":1768803350607,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>Transactive response DNA\u2010binding protein 43 (TDP\u201043) pathological inclusions are found in frontotemporal lobar degeneration (FTLD\u2010TDP) and Alzheimer's disease (AD\u2010TDP). While clinically different, TDP\u201043 inclusions in FTLD\u2010TDP and AD can have similar morphological characteristics. However, TDP\u201043 colocalizing with tau and forming \u201capple\u2010bite\u201d or \u201cflame\u2010shaped\u201d neuronal cytoplasmic inclusions (NCI) are only found in AD\u2010TDP. Here, we describe a case with AD and neuritic plaque\u2010associated TDP\u201043. The patient was a 96\u2010year\u2010old right\u2010handed Caucasian woman who had developed a slowly progressive amnestic syndrome compatible with typical AD at age 80. Genetic testing revealed <jats:italic>APOE \u03b53\/\u03b54<\/jats:italic>, <jats:italic>GRN<\/jats:italic> r5848 CT, and <jats:italic>MAPT<\/jats:italic> H1\/H2 genotype. Consistent with the old age at onset and long disease duration, limbic\u2010predominant AD was found at autopsy, with high hippocampal yet low cortical neurofibrillary tangle (NFT) counts. Hippocampal and amygdala sclerosis were present. Immunohistochemistry for phospho\u2010TDP\u201043 showed NCIs, dystrophic neurites, and rare neuronal intranuclear inclusions consistent with FTLD\u2010TDP type A, as well as tau NFT\u2010associated TDP\u201043 inclusions. These were frequent in the amygdala, entorhinal cortex, hippocampus, occipitotemporal gyrus, and inferior temporal gyrus but sparse in the mid\u2010frontal cortex. Additionally, there were TDP\u201043\u2010immunoreactive inclusions forming plaque\u2010like structures in the molecular layer of the dentate fascia of the hippocampus. The presence of neuritic plaques in the same region was confirmed using thioflavin\u2010S fluorescent microscopy and immunohistochemistry for phospho\u2010tau. Double labeling immunofluorescence showed colocalization of TDP\u201043 and tau within neuritic plaques. Other pathologies included mild Lewy body pathology predominantly affecting the amygdala and olfactory bulb, aging\u2010related tau astrogliopathy, and mixed small vessel disease (arteriolosclerosis and amyloid angiopathy) with several cortical microinfarcts. In conclusion, we have identified TDP\u201043 colocalizing with tau in neuritic plaques in AD, which expands the association of TDP\u201043 and tau in AD beyond NFTs. The clinical correlate of this plaque\u2010associated TDP\u201043 appears to be a slowly progressive amnestic syndrome.<\/jats:p>","DOI":"10.1111\/neup.12938","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T03:55:09Z","timestamp":1690862109000},"page":"115-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Senile plaque\u2010associated transactive response DNA\u2010binding protein 43 in Alzheimer's disease: A case report spanning 16\u2009years of memory loss"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-5033","authenticated-orcid":false,"given":"Arenn F.","family":"Carlos","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota 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