Caspase-2 mRNA levels are not elevated in mild cognitive impairment, Alzheimer's disease, Huntington's disease, or Lewy Body dementia

PLoS One. 2022 Sep 21;17(9):e0274784. doi: 10.1371/journal.pone.0274784. eCollection 2022.


Caspase-2 is a member of the caspase family that exhibits both apoptotic and non-apoptotic properties, and has been shown to mediate synaptic deficits in models of several neurological conditions, including Alzheimer's disease (AD), Huntington's disease (HD), and Lewy Body dementia (LBD). 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 βIII-tubulin mRNA. SNAP25 mRNA was significantly lower in AD and there were downward trends in MCI, LBD, and HD. βIII-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / psychology
  • Caspase 2 / genetics*
  • Cognitive Dysfunction* / etiology
  • Cysteine Endopeptidases / genetics*
  • Humans
  • Huntington Disease* / complications
  • Huntington Disease* / genetics
  • Lewy Body Disease* / complications
  • Neoplasm Proteins
  • RNA Isoforms
  • RNA, Messenger / genetics
  • Ribosomal Proteins
  • Tubulin


  • Neoplasm Proteins
  • RNA Isoforms
  • RNA, Messenger
  • RPL13 protein, human
  • Ribosomal Proteins
  • Tubulin
  • CASP2 protein, human
  • Caspase 2
  • Cysteine Endopeptidases