title: 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.
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.
authors.affiliation: Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore. Mei_Sian_Chong@ttsh.com.sg
authors.forename: Mei Sian
authors.initials: MS
authors.lastname: Chong
authors.forename: Liang Kee
authors.initials: LK
authors.lastname: Goh
authors.forename: Wee Shiong
authors.initials: WS
authors.lastname: Lim
authors.forename: Mark
authors.initials: M
authors.lastname: Chan
authors.forename: Laura
authors.initials: L
authors.lastname: Tay
authors.forename: Gengbo
authors.initials: G
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Tze Pin
authors.initials: TP
authors.lastname: Ng
authors.forename: Chay Hoon
authors.initials: CH
authors.lastname: Tan
authors.forename: Tih Shih
authors.initials: TS
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology*; D042241:Early Diagnosis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D051246:Glucose Transport Proteins, Facilitative / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000096:biosynthesis* / Q000235:genetics; D011446:Prospective Studies; D054346:Receptors, KIR2DL5 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D015415:Biomarkers; D051246:Glucose Transport Proteins, Facilitative; C515080:KIR2DL5A protein, human; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D054346:Receptors, KIR2DL5; C405325:SLC2A8 protein, human; C400783:TOMM40 protein, human; C572044:PLOD1 protein, human; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase