You are viewing a javascript disabled version of the site. Please enable Javascript for this site to function properly.
Go to headerGo to navigationGo to searchGo to contentsGo to footer
In content section. Select this link to jump to navigation

Plasma Transthyretin as a Candidate Marker for Alzheimer's Disease

Article type: Research Article

Authors: Velayudhan, Lathaa; d; * | Killick, Richarda | Hye, Abdula | Kinsey, Annaa | Güntert, Andreasa | Lynham, Stevena | Ward, Malcolmb | Leung, Rufinaa | Lourdusamy, Anbarasuc | To, Alvina W.M.a | Powell, Johna | Lovestone, Simona

Affiliations: [a] Department of Old Age Psychiatry, NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London and the MRC Centre for Neurodegeneration, King's College London, Institute of Psychiatry, London, UK | [b] Proteome Sciences plc, Surrey, UK | [c] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK | [d] Department of Health Sciences, University of Leicester, Leicester, UK

Correspondence: [*] Correspondence to: Dr. Latha Velayudhan, P.O. Box 70, Department of Old Age Psychiatry, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. Tel.: +44 (0)2078480508; Fax: +44 (0)2078480632; E-mails: [email protected] and [email protected].

Keywords: Alzheimer's disease, cognitive impairment, plasma proteins, transthyretin

DOI: 10.3233/JAD-2011-110611

Journal: Journal of Alzheimer's Disease, vol. 28, no. 2, pp. 369-375, 2012

Accepted 5 September 2011
|
Published: 25 January 2012
Get PDF open access
Supplementary Materials:

Supplementary Materials.

Abstract

Diagnosis of the progressive neurodegenerative disorder Alzheimer's disease (AD) can only definitively be made postmortem. The most promising AD biomarkers identified to date are found in cerebrospinal fluid (CSF). Among these, one of the most interesting candidates is transthyretin (TTR), the carrier of thyroxine and retinol, which also binds with amyloid-β (Aβ), and it has been suggested that it protects against Aβ deposition. A biomarker detectable in plasma would have great diagnostic value and could be of use for determining disease progression and the monitoring of therapeutic efficacy due to its greater accessibility over CSF-based markers. We aimed to validate TTR as a prognostic marker in AD and to determine its relation with cognitive measures. We examined the plasma protein levels of TTR in 90 people with late-onset AD and 50 age-matched non-demented controls (NDC) by immunoblotting and found lower plasma TTR levels in AD compared to NDC (p = 0.004). We then quantified plasma TTR by enzyme-linked immunosorbent assays in a larger independent cohort (n = 270) including subjects with mild to severe AD. Plasma TTR levels were significantly lower in AD cases with rapid cognitive decline and with severe cognitive impairment. Regression analyses showed plasma TTR levels also predicted cognitive decline over the ensuing 6 months. These data indicate that plasma TTR is a strong candidate AD biomarker that should be included in the development of blood based biomarker panels for disease diagnosis and also suggests that plasma TTR is a marker of disease severity and progression.

Show more