No association of CSF biomarkers with APOE epsilon 4, plaque and tangle burden in definite Alzheimer's disease

• Published in: Brain (London, England : 1878) England : 1878), 2007-09, Vol.130 (9), p.2320-2326
• Main Authors: Engelborghs, Sebastiaan, Sleegers, Kristel, Cras, Patrick, Brouwers, Nathalie, Serneels, Sally, De Leenheir, Evelyn, Martin, Jean-Jacques, Vanmechelen, Eugeen, Van Broeckhoven, Christine, De Deyn, Peter Paul
• Format: Article
• Language: English
• ISSN: 0006-8950
• DOI: 10.1093/brain/awm136

The CSF biomarkers {szligbeta}-amyloid peptide (A{szligbeta} sub(1-42)), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau sub(181P)) were determined in autopsy-confirmed Alzheimer's disease patients in order to study possible associations with the epsilon 4 allele of APOE and density and spread of plaques (SP) and tangles (NFT). CSF levels of A{szligbeta} sub(1-42), T-tau and P-tau sub(181P) were determined in 50 Alzheimer's disease patients using commercially available single parameter ELISA kits (INNOTEST registered ). Genomic DNA was extracted from whole blood and the APOE genotype was determined using standard methods. Tangle burden was assessed by means of Braak's NFT stages (I-VI), whereas the plaque burden was assessed by means of Braak's SP stages (A-C). CSF biomarker levels were not different when comparing epsilon 4 carriers (n = 21) and non-carriers (n = 29) (P > 0.05 for all comparisons). No significant correlations between the number of epsilon 4 alleles (0, 1 or 2) and CSF levels of A{szligbeta} sub(1-42) (Spearman Rank Order: r = -0.057, P = 0.695), T-tau (r = 0.104, P = 0.472) and P-tau sub(181P) (r = 0.062, P = 0.668) were found. Braak's SP (A{szligbeta} sub(1-42): r = -0.155, P = 0.280; T-tau: r = -0.044, P = 0.763; P-tau sub(181P): r = -0.010, P = 0.947) and NFT (A{szligbeta} sub(1-42): r = -0.145, P = 0.315; T-tau: r = 0.117, P = 0.415; P-tau sub(181P): r = 0.150, P = 0.296) stages were not significantly correlated with CSF biomarker levels. In conclusion, CSF levels of A{szligbeta} sub(1-42), T-tau and P-tau sub(181P) were not associated with epsilon 4, tangle or plaque burden in 50 autopsy-confirmed Alzheimer's disease patients. In the light of future biomarker applications like monitoring of disease progression and as allocortical neuropathological changes significantly contribute to clinical symptoms, the concept of in vivo surrogate biomarkers should be further explored.