CSF Aβ_1-42 Levels and Glucose Metabolism in Alzheimer's Disease>

Article type: Research Article

Authors: Dumurgier, Julien^{a; b; *} | Paquet, Claire^{a; c; d} | Peoc'h, Katell^e | Lapalus, Pauline^a | Mouton-Liger, François^{c; d} | Benisty, Sarah^a | Chasseigneaux, Stéphanie^e | Chabriat, Hughes^f | Hugon, Jacques^{a; c; d}

Affiliations: [a] Centre Mémoire de Ressources et de Recherche (CMRR) Paris Nord Ile-de-France, Lariboisière - Fernand Widal Hospital, APHP, University Paris 7-Denis Diderot, Paris, France | [b] INSERM Neuroepidemiology, Hôpital la Salpêtrière, Paris, France | [c] Department of Histology and Biology of Aging, Lariboisière - Fernand Widal Hospital, APHP, University Paris 7-Denis Diderot, Paris, France | [d] INSERM, Institut du Fer à Moulin, Paris, France | [e] Department of Biochemistry, Lariboisière - Fernand Widal Hospital, APHP, University Paris 7-Denis Diderot, Paris, France | [f] Department of Neurology, Lariboisière - Fernand Widal Hospital, APHP, University Paris 7-Denis Diderot, Paris, France

Correspondence: [*] Correspondence to: Julien Dumurgier, CMRR Paris Nord-IDF, 200 rue du Faubourg Saint Denis, 75010 Paris, France. Tel.: +33 1 40 05 49 54; Fax: +33 1 40 05 43 39; E-mail: [email protected].

Abstract: Glucose dysmetabolism has been consistently associated with an increased risk of cognitive disorders, and brain insulin resistance could play a role in Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We have investigated the relationship between CSF concentrations of amyloid-β peptide 1-42 (Aβ1-42), total tau, and phosphorylated tau (ptau-181) and plasma and CSF glucose levels in a cohort of 94 newly diagnosed non-diabetics AD patients. We report that CSF Aβ1-42 level was inversely associated with CSF to plasma glucose ratio (Spearman's coefficient = −0.27, p = 0.008). This relationship remained after adjustment for age, gender, body mass index, hypertension, and MMSE score (β [SE] of linear regression = −0.93 [0.37], p = 0.01). In stratified analysis, this relationship was observed only in patients who did not carry the apolipoprotein E4 allele. No significant relationship was found between glucose levels and total tau or phosphorylated tau 181. These results support the idea that a link between glucose dysmetabolism and the amyloid pathway may exist in the pathogenesis of AD.

Keywords: Alzheimer's disease, amyloid-β peptide, biomarkers, CSF, glucose

DOI: 10.3233/JAD-2011-111007

Journal: Journal of Alzheimer's Disease, vol. 27, no. 4, pp. 845-851, 2011