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Our lab previously reported that caspase-2 protein levels are elevated in these diseases, leading us to hypothesize that elevated caspase-2 protein levels are due to increased transcription of caspase-2 mRNA. There are two major isoforms of caspase-2 mRNA, caspase-2L and caspase-2S. We tested our hypothesis by measuring the levels of these mRNA isoforms normalized to levels of RPL13 mRNA, a reference gene that showed no disease-associated changes. Here, we report no increases in caspase-2L mRNA levels in any of the three diseases studied, AD (with mild cognitive impairment (MCI)), HD and LBD, disproving our hypothesis. Caspase-2S mRNA showed a non-significant downward trend in AD. We also analyzed expression levels of SNAP25 and \u03b2III-tubulin mRNA. SNAP25 mRNA was significantly lower in AD and there were downward trends in MCI, LBD, and HD. \u03b2III-tubulin mRNA expression remained unchanged between disease groups and controls. These findings indicate that factors besides transcriptional regulation cause increases in caspase-2 protein levels. The reduction of SNAP25 mRNA expression suggests that presynaptic dysfunction contributes to cognitive deficits in neurodegeneration.<\/jats:p>","DOI":"10.1371\/journal.pone.0274784","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T17:39:21Z","timestamp":1663781961000},"page":"e0274784","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Caspase-2 mRNA levels are not elevated in mild cognitive impairment, Alzheimer\u2019s disease, Huntington\u2019s disease, or Lewy Body dementia"],"prefix":"10.1371","volume":"17","author":[{"given":"Chris","family":"Hlynialuk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Kemper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kailee","family":"Leinonen-Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald C.","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Ashe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-9455","authenticated-orcid":true,"given":"Benjamin","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"issue":"4","key":"pone.0274784.ref001","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/sj.cdd.4400989","article-title":"Alice in caspase land. 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