Gene expression profiling of peripheral blood leukocytes shows consistent longitudinal downregulation of TOMM40 and upregulation of KIR2DL5A, PLOD1, and SLC2A8 among fast progressors in early Alzheimer's disease

Mei Sian Chong; Liang Kee Goh; Wee Shiong Lim; Mark Chan; Laura Tay; Gengbo Chen; Lei Feng; Tze Pin Ng; Chay Hoon Tan; Tih Shih Lee

doi:10.3233/JAD-121621

Gene expression profiling of peripheral blood leukocytes shows consistent longitudinal downregulation of TOMM40 and upregulation of KIR2DL5A, PLOD1, and SLC2A8 among fast progressors in early Alzheimer's disease

J Alzheimers Dis. 2013;34(2):399-405. doi: 10.3233/JAD-121621.

Authors

Mei Sian Chong¹, Liang Kee Goh, Wee Shiong Lim, Mark Chan, Laura Tay, Gengbo Chen, Lei Feng, Tze Pin Ng, Chay Hoon Tan, Tih Shih Lee

Affiliation

¹ Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore. Mei_Sian_Chong@ttsh.com.sg

PMID: 23234877
DOI: 10.3233/JAD-121621

Abstract

We previously reported TOMM40 was significantly down-regulated in whole blood of Alzheimer's disease (AD) subjects. In this study, we examined whole blood gene profiling differences over a one-year period comparing early AD subjects based on disease progression. 6-monthly assessments and blood sampling on 29 probable AD subjects compared with age- and gender-matched controls were performed. AD subjects with change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score of ≥2 points/year were classified as fast-progressors and those with CDR-SB change of <2 points/year were classified as slow-progressors. We found statistically significant upregulation in KIR2DL5A, SLC2A8, and PLOD1 for fast- (n = 8) compared with slow-progressors (n = 21) across the time-points. TOMM40 gene expression remained significantly lower in AD patients at all time-points compared to controls, supporting our previous findings. Our novel findings of specific gene expression differences between fast- and slow-progressors in combination with consistently lower TOMM40 expression, suggest their potential role as prognostic blood biomarkers to predict progression in early AD.

Publication types

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

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / blood*
Alzheimer Disease / diagnosis
Alzheimer Disease / genetics
Biomarkers / blood
Disease Progression
Down-Regulation / physiology*
Early Diagnosis
Female
Gene Expression Profiling / methods
Glucose Transport Proteins, Facilitative / biosynthesis*
Glucose Transport Proteins, Facilitative / genetics
Humans
Leukocytes, Mononuclear / metabolism*
Longitudinal Studies
Male
Membrane Transport Proteins / genetics
Membrane Transport Proteins / metabolism*
Mitochondrial Precursor Protein Import Complex Proteins
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / biosynthesis*
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
Prospective Studies
Receptors, KIR2DL5 / biosynthesis*
Receptors, KIR2DL5 / genetics
Up-Regulation / physiology*

Substances

Biomarkers
Glucose Transport Proteins, Facilitative
KIR2DL5A protein, human
Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Receptors, KIR2DL5
SLC2A8 protein, human
TOMM40 protein, human
PLOD1 protein, human
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase