Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer's disease

Young Ho Park; Jung-Min Pyun; Angela Hodges; Jae-Won Jang; Paula J Bice; SangYun Kim; Andrew J Saykin; Kwangsik Nho; AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative

doi:10.1186/s13195-021-00919-z

Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer's disease

Alzheimers Res Ther. 2021 Nov 3;13(1):183. doi: 10.1186/s13195-021-00919-z.

Authors

Young Ho Park¹, Jung-Min Pyun², Angela Hodges³, Jae-Won Jang⁴, Paula J Bice⁵, SangYun Kim¹, Andrew J Saykin^{5

6}, Kwangsik Nho^{7

8}; AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.
² Department of Neurology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, Republic of Korea.
³ Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Department of Neurology, Kangwon National University Hospital, Chuncheon, Republic of Korea.
⁵ Department of Radiology and Imaging Sciences, and the Indiana Alzheimer Disease Center, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁷ Department of Radiology and Imaging Sciences, and the Indiana Alzheimer Disease Center, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA. knho@iu.edu.
⁸ Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA. knho@iu.edu.

Abstract

Background: The interaction between the brain and periphery might play a crucial role in the development of Alzheimer's disease (AD).

Methods: Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 significant genetic loci from a recent large-scale genome-wide association study to investigate the effects of the AD genetic variants on gene expression levels and identify their potential target genes. We then performed differential gene expression analysis of identified AD target genes and linear regression analysis to evaluate the association of differentially expressed genes with neuroimaging biomarkers.

Results: A cis-eQTL analysis identified and replicated significant associations in seven genes (APH1B, BIN1, FCER1G, GATS, MS4A6A, RABEP1, TRIM4). APH1B expression levels in the blood increased in AD and were associated with entorhinal cortical thickness and global cortical amyloid-β deposition.

Conclusion: An integrative analysis of genetics, blood-based transcriptomic profiles, and imaging biomarkers suggests that APH1B expression levels in the blood might play a role in the pathogenesis of AD.

Keywords: Alzheimer’s disease; Blood; Expression; Expression quantitative trait locus; Genome-wide association study; Imaging; Transcriptome.

Publication types

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

MeSH terms

Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / genetics
Alzheimer Disease* / pathology
Amyloid beta-Protein Precursor* / metabolism
Atrophy / pathology
Brain / diagnostic imaging
Brain / pathology
Endopeptidases* / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Membrane Proteins* / genetics
Transcriptome

Substances

APP protein, human
Amyloid beta-Protein Precursor
Membrane Proteins
APH1B protein, human
Endopeptidases

Abstract

Publication types

MeSH terms

Substances

Grants and funding