{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:56:53Z","timestamp":1792673813998,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T00:00:00Z","timestamp":1177632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD\u2010U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP\u201043), a putative marker for FTLD\u2010U.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD\u2010U with TDP\u201043 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP\u201043 antibodies was assessed using double\u2010immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TDP\u201043 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP\u201043 and phospho\u2010tau showed that the TDP\u201043\u2013immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP\u201043 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP\u201043 that was not present in AD cases without TDP\u201043 immunoreactivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD\u2010U. Whether this represents concomitant FTLD\u2010U or is analogous to colocalization of \u03b1\u2010synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined. Ann Neurol 2007;61:435\u2013445<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21154","type":"journal-article","created":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T20:47:07Z","timestamp":1177706827000},"page":"435-445","source":"Crossref","is-referenced-by-count":833,"title":["TDP\u201043 immunoreactivity in hippocampal sclerosis and Alzheimer's 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