Human Serum Transthyretin Levels Correlate Inversely with Alzheimer's Disease

Article type: Research Article

Authors: Han, Sun-Ho^{a; 1} | Jung, Eun Sun^{a; 1} | Sohn, Ji-Hoon^a | Hong, Hyun Joo^a | Hong, Hyun Seok^e | Kim, Jong Won^b | Na, Duk Lyul^c | Kim, Manho^d | Kim, Hee^e | Ha, Hee Jin^e | Kim, Young Ho^e | Huh, Namjung^f | Jung, Min Whan^f | Mook-Jung, Inhee^{a; *}

Affiliations: [a] Department of Biochemistry and Biomedical Science, Seoul National University, College of Medicine, Seoul, Korea | [b] Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea | [c] Department of Neurology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea | [d] Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea | [e] Digital Biotech, Inc., Gyeongi, Korea | [f] Biomedical Science Institute, Ajou University, School of Medicine, Suwon, Korea

Correspondence: [*] Correspondence to: Inhee Mook-Jung, PhD, Department of Biochemistry and Biomedical Science, Seoul National University, College of Medicine, 28 Yungun-dong, Jongro-gu, Seoul 110-799, Korea. Tel.: +82 2 740 8245; Fax: +82 2 3672 7352; E-mail: inhee@snu.ac.kr.

Note: [1] Contributed equally to this report.

Abstract: Alzheimer's disease (AD) is the fastest growing neurodegenerative disease in the elderly population, and the search for therapeutic targets and diagnostic AD biomarkers is an exigent issue. Because amyloid-β (Aβ) aggregation constitutes the epicenter of AD pathology, Aβ-binding proteins that regulate Aβ aggregation, such as transthyretin (TTR), have attracted much attention. TTR binds to Aβ, prevents its aggregation, and consequently inhibits Aβ-induced cellular toxicity. Decreased TTR levels in cerebrospinal fluid (CSF) from AD patients suggest that TTR is a biomarker of AD. But, studies on TTR as a biomarker have focused on CSF; no study has evaluated peripheral levels of TTR in AD. Here, we examined the relationship between serum TTR levels and AD. We measured TTR levels in serum samples from 90 nondemented controls and 111 AD patients and observed significantly lower serum TTR levels in AD (p < 0.001). Notably, females in the control group had lower serum TTR levels compared with male in the control (p = 0.006), while no difference in gender was noted in the AD group. There were no age-related changes in serum TTR levels. Thus, this study demonstrates a clear negative correlation between serum TTR levels and AD, suggesting that TTR is not only involved in AD pathological process but also suggested as possible peripheral biomarker for AD diagnosis in serum level.

Keywords: Alzheimer's disease, amyloid-β aggregation, biomarker, serum, transthyretin

DOI: 10.3233/JAD-2011-102145

Journal: Journal of Alzheimer's Disease, vol. 25, no. 1, pp. 77-84, 2011