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In Alzheimer\u2019s disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (\n                    <jats:italic>STMN2<\/jats:italic>\n                    , also known as\n                    <jats:italic>SCG10<\/jats:italic>\n                    ) and\n                    <jats:italic>UNC13A<\/jats:italic>\n                    , recently reported in tissues from patients with ALS and FTD. Here, we identify both\n                    <jats:italic>STMN2<\/jats:italic>\n                    and\n                    <jats:italic>UNC13A<\/jats:italic>\n                    cryptic exons in Alzheimer\u2019s disease patients, that correlate with TDP-43 pathology burden, but not with amyloid-\u03b2 or tau deposits. We also demonstrate that processing of the\n                    <jats:italic>STMN2<\/jats:italic>\n                    pre-mRNA is more sensitive to TDP-43 loss of function than\n                    <jats:italic>UNC13A<\/jats:italic>\n                    . In addition, full-length RNAs encoding\n                    <jats:italic>STMN2<\/jats:italic>\n                    and\n                    <jats:italic>UNC13A<\/jats:italic>\n                    are suppressed in large RNA-seq datasets generated from Alzheimer\u2019s disease post-mortem brain tissue. Collectively, these results open exciting new avenues to use\n                    <jats:italic>STMN2<\/jats:italic>\n                    and\n                    <jats:italic>UNC13A<\/jats:italic>\n                    as potential therapeutic targets in a broad range of neurodegenerative conditions with TDP-43 proteinopathy including Alzheimer\u2019s disease.\n                  <\/jats:p>","DOI":"10.1007\/s00401-023-02655-0","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T10:02:37Z","timestamp":1704362557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"147","author":[{"given":"Ana Rita","family":"Agra Almeida Quadros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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