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

Article type: Research Article

Authors: Chong, Mei Sian^{a; *; 1} | Goh, Liang Kee^{b; 1} | Lim, Wee Shiong^a | Chan, Mark^a | Tay, Laura^a | Chen, Gengbo^b | Feng, Lei^c | Ng, Tze Pin^c | Tan, Chay Hoon^d | Lee, Tih Shih^{b; e}

Affiliations: [a] Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore | [b] Duke-NUS Graduate Medical School, Singapore | [c] Gerontological Research Programme, Department of Psychological Medicine, National University of Singapore, Singapore | [d] Department of Pharmacology, National University Health System, Singapore | [e] Department of Psychiatry and Behavioral Science, Duke University Medical School, Durham, NC, USA

Correspondence: [*] These authors contributed equally. Correspondence to: Mei Sian Chong, Department of Geriatric Medicine, 11 Jalan Tan Tock Seng, S308433, Singapore. Tel.: +65 63577859; Fax: +65 63577837; E-mail: Mei_Sian_Chong@ttsh.com.sg.

Note: [1] These authors contributed equally.

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.

Keywords: Alzheimer's disease, gene expression, progression, TOMM40

DOI: 10.3233/JAD-121621

Journal: Journal of Alzheimer's Disease, vol. 34, no. 2, pp. 399-405, 2013