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

Chris Hlynialuk; Lisa Kemper; Kailee Leinonen-Wright; Ronald C. Petersen; Karen Ashe; Benjamin Smith

doi:10.1371/journal.pone.0274784

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

Chris Hlynialuk, Lisa Kemper, Kailee Leinonen-Wright, Ronald C. Petersen, Karen Ashe, Benjamin Smith

Neurology

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e0274784
Journal	PloS one
Volume	17
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0274784
State	Published - Sep 2022

Bibliographical note

Funding Information:
Sources of funding for this study include the T. and P. Grossman Family Foundation (K.H. A.), B. Grossman (K.H.A.) and K. Moe (K.H.A.), ADRC and MCSA of the Mayo Clinic (funding supported by National institutes of Health; NIA: U01 AG006786, P30AG062677, R01AG034676). funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Jean P. Vonsattel (Columbia University) for supplying HD samples and Dr. Dirk Keene (Washington University) for supplying LBD samples. We also acknowledge our collaboration Dr. David Knopman and the ADRC and MCSA of the Mayo Clinic for supplying AD/MCI samples.

Publisher Copyright:
© 2022 Hlynialuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

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

PubMed: MeSH publication types

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1371/journal.pone.0274784

Find It

Find It at U of M Libraries

Cite this

@article{65d5b6483dfb4f1a843bd22864984c83,

title = "Caspase-2 mRNA levels are not elevated in mild cognitive impairment, Alzheimer{\textquoteright}s disease, Huntington{\textquoteright}s disease, or Lewy Body dementia",

abstract = "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{\textquoteright}s disease (AD), Huntington{\textquoteright}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.",

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

author = "Chris Hlynialuk and Lisa Kemper and Kailee Leinonen-Wright and Petersen, {Ronald C.} and Karen Ashe and Benjamin Smith",

note = "Funding Information: Sources of funding for this study include the T. and P. Grossman Family Foundation (K.H. A.), B. Grossman (K.H.A.) and K. Moe (K.H.A.), ADRC and MCSA of the Mayo Clinic (funding supported by National institutes of Health; NIA: U01 AG006786, P30AG062677, R01AG034676). funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Jean P. Vonsattel (Columbia University) for supplying HD samples and Dr. Dirk Keene (Washington University) for supplying LBD samples. We also acknowledge our collaboration Dr. David Knopman and the ADRC and MCSA of the Mayo Clinic for supplying AD/MCI samples. Publisher Copyright: {\textcopyright} 2022 Hlynialuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2022",

month = sep,

doi = "10.1371/journal.pone.0274784",

language = "English (US)",

volume = "17",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

TY - JOUR

T1 - Caspase-2 mRNA levels are not elevated in mild cognitive impairment, Alzheimer’s disease, Huntington’s disease, or Lewy Body dementia

AU - Hlynialuk, Chris

AU - Kemper, Lisa

AU - Leinonen-Wright, Kailee

AU - Petersen, Ronald C.

AU - Ashe, Karen

AU - Smith, Benjamin

N1 - Funding Information: Sources of funding for this study include the T. and P. Grossman Family Foundation (K.H. A.), B. Grossman (K.H.A.) and K. Moe (K.H.A.), ADRC and MCSA of the Mayo Clinic (funding supported by National institutes of Health; NIA: U01 AG006786, P30AG062677, R01AG034676). funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Jean P. Vonsattel (Columbia University) for supplying HD samples and Dr. Dirk Keene (Washington University) for supplying LBD samples. We also acknowledge our collaboration Dr. David Knopman and the ADRC and MCSA of the Mayo Clinic for supplying AD/MCI samples. Publisher Copyright: © 2022 Hlynialuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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.

KW - Alzheimer Disease/psychology

KW - Caspase 2/genetics

KW - Cognitive Dysfunction/etiology

KW - Cysteine Endopeptidases/genetics

KW - Humans

KW - Huntington Disease/complications

KW - Lewy Body Disease/complications

KW - Neoplasm Proteins

KW - RNA Isoforms

KW - RNA, Messenger/genetics

KW - Ribosomal Proteins

KW - Tubulin

UR - http://www.scopus.com/inward/record.url?scp=85138457885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85138457885&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0274784

DO - 10.1371/journal.pone.0274784

M3 - Article

C2 - 36129947

AN - SCOPUS:85138457885

SN - 1932-6203

VL - 17

JO - PloS one

JF - PloS one

IS - 9

M1 - e0274784

ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this