Alterations in the Expression of Amyloid Precursor Protein Cleaving Enzymes mRNA in Alzheimer Peripheral Blood

Prapimpun Wongchitrat; Nattaporn Pakpian; Kuntida Kitidee; Kamonrat Phopin; Pornpatr A Dharmasaroja; Piyarat Govitrapong

doi:10.2174/1567205015666181109103742

Alterations in the Expression of Amyloid Precursor Protein Cleaving Enzymes mRNA in Alzheimer Peripheral Blood

Curr Alzheimer Res. 2019;16(1):29-38. doi: 10.2174/1567205015666181109103742.

Authors

Prapimpun Wongchitrat¹, Nattaporn Pakpian², Kuntida Kitidee¹, Kamonrat Phopin¹, Pornpatr A Dharmasaroja³, Piyarat Govitrapong^{2

4}

Affiliations

¹ Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakon Pathom, Thailand.
² Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakon Pathom, Thailand.
³ Stroke and Neurodegenerative Diseases Research Unit, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
⁴ Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand.

PMID: 30411686
DOI: 10.2174/1567205015666181109103742

Abstract

Background: Alzheimer's disease (AD) is the most common cause of dementia in elderly populations. Changes in the expression of the Amyloid Precursor Protein (APP)-cleaving enzymes directly affect the formation of Amyloid Beta (Aβ) plaques, a neuropathological hallmark of AD.

Objective: We used peripheral blood from AD patients to investigate the expression of genes related to APP-processing [(β-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), and a disintegrin and metalloproteinase family 10 (ADAM10) and 17 (ADAM17)] and the epigenetic genes sirtuin (SIRT)1-3, which regulate Aβ production.

Method: Real-time polymerase chain reactions were performed to determine the specific mRNA levels in plasma. The mRNA levels in AD patients were compared to those in healthy persons and assessed in relation to the subjects' cognitive performance.

Results: BACE1 mRNA level in AD subjects was significantly higher than those of healthy controls, whereas ADAM10 level was significantly lower in the AD subjects. The SIRT1 level was significantly decreased, while that of SIRT2 was increased in AD subjects and elderly controls compared to levels in healthy young control. In addition, correlations were found between the expression levels of BACE1, ADAM10 and SIRT1 and cognitive performance scores. Total Aβ (Aβ40+Aβ42) levels and the Aβ40/Aβ42 ratio were significantly increased in the AD subjects, whereas decrease in plasma Aβ42 was found in AD subjects. There was a negative correlation between Aβ40 or total Aβ and Thai Mental State Examination (TMSE) while there was no correlation between Aβ40/Aβ42 ratio or Aβ42 and TMSE.

Conclusion: The present findings provide evidence and support for the potential roles of these enzymes that drive Aβ synthesis and for epigenetic regulation in AD progression and development, which can possibly be considered peripheral markers of AD.

Keywords: APP-cleaving enzymes; Alzheimer's disease; amyloid beta; gene expression; plasma biomarkers; sirtuins..

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADAM Proteins / blood*
Adult
Aged
Alzheimer Disease / blood*
Alzheimer Disease / enzymology*
Alzheimer Disease / psychology
Amyloid Precursor Protein Secretases / blood*
Amyloid beta-Peptides / blood
Aspartic Acid Endopeptidases / blood*
Biomarkers / blood
Cognition
Female
Gene Expression
Humans
Male
Peptide Fragments / blood
Presenilin-1 / blood*
RNA, Messenger / blood
Sirtuins / blood*

Substances

Amyloid beta-Peptides
Biomarkers
PSEN1 protein, human
Peptide Fragments
Presenilin-1
RNA, Messenger
amyloid beta-protein (1-40)
amyloid beta-protein (1-42)
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
BACE1 protein, human
ADAM Proteins
Sirtuins