Plasma Amyloid-β Levels and Prognosis in Incident Dementia Cases of the 3-City Study

Article type: Research Article

Authors: Gabelle, Audrey^{a; b; c; *} | Richard, Florence^{d; e; f} | Gutierrez, Laure-Anne^g | Schraen, Susanna^{f; h} | Delva, Fleurⁱ | Rouaud, Olivier^j | Buée, Luc^{f; h} | Dartigues, Jean-Françoisⁱ | Touchon, Jacques^{a; c; g} | Lambert, Jean-Charles^{d; e} | Berr, Claudine^{a; c; g}

Affiliations: [a] Department of Neurology, Centre Mémoire Ressources Recherche Languedoc-Roussillon, CHRU Gui de Chauliac Hospital, Montpellier, France | [b] INSERM-UM1 U1040, IRB, Saint Eloi Hospital, Montpellier, France | [c] University Montpellier 1, Montpellier, France | [d] INSERM U744, Lille, France, and Institut Pasteur de Lille, France | [e] Université de Lille Nord de France, Lille, France | [f] CHRU de Lille, Lille, France | [g] INSERM U1061, La Colombière Hospital, Montpellier, France | [h] INSERM U837, Lille, France | [i] INSERM U897, Victor Segalen University, Bordeaux, France | [j] Department of Neurology, CMRR de Dijon, CHRU Dijon, Dijon, France

Correspondence: [*] Correspondence to: Dr. Audrey Gabelle, MD, PhD, CMRR Montpellier, CHRU Gui de Chauliac, Department of Neurology, F-34295 Montpellier Cedex 5, France. Tel.: +33 46733 7947; Fax: +33 46733 6036; E-mail: [email protected].

Abstract: Studies of plasma amyloid-β (Aβ) levels as potential biomarkers for incident Alzheimer's disease (AD) have yielded contradictory results. We explored the associations between plasma Aβ40, Aβ42, and truncated Aβ levels, and prognosis of dementia in participants of the prospective 3-City Study. 120 aged individuals diagnosed with 2-year incident dementia were followed up for seven years. The associations between Aβ plasma levels and baseline cognitive score, cognitive decline, and death were examined. A higher level of baseline plasma Aβ was associated with worse cognitive status two years prior to incident dementia diagnosis. In incident AD patients, the association was only significant for Aβ40 and Aβn-42. In the fast cognitive decliners group, especially in AD cases, a higher level of 5 pg/ml of baseline Aβ42, Aβn-42, Aβn-42/Aβn-40, and Aβ42/Aβ40 ratios were associated with a lower risk of fast cognitive decline based on the Isaacs Set Test score. There was no association between peptide levels and mortality in demented subjects. When assayed at prodromal stage, plasma Aβ levels may be potentially useful markers of fast cognitive decline in individuals who subsequently become demented.

Keywords: Alzheimer's disease, cohort studies, mild cognitive impairment, plasma amyloid-β peptides

DOI: 10.3233/JAD-2012-121147

Journal: Journal of Alzheimer's Disease, vol. 33, no. 2, pp. 381-391, 2013