title: Plasma transthyretin as a candidate marker for Alzheimer's disease.
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.
authors: Department of Old Age Psychiatry, NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust, London, UK. Velayudhan@kcl.ac.uk
authors: Latha
authors: L
authors: Velayudhan
authors: Richard
authors: R
authors: Killick
authors: Abdul
authors: A
authors: Hye
authors: Anna
authors: A
authors: Kinsey
authors: Andreas
authors: A
authors: Güntert
authors: Steven
authors: S
authors: Lynham
authors: Malcolm
authors: M
authors: Ward
authors: Rufina
authors: R
authors: Leung
authors: Anbarasu
authors: A
authors: Lourdusamy
authors: Alvina W M
authors: AW
authors: To
authors: John
authors: J
authors: Powell
authors: Simon
authors: S
authors: Lovestone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000235:genetics; D001057:Apolipoproteins E; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D008609:Mental Status Schedule; D011228:Prealbumin / Q000378:metabolism*; D044465:White People
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D011228:Prealbumin