title: No association of CSF biomarkers with APOEepsilon4, plaque and tangle burden in definite Alzheimer's disease.
abstract: The CSF biomarkers beta-amyloid peptide (Abeta(1-42)), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau(181P)) were determined in autopsy-confirmed Alzheimer's disease patients in order to study possible associations with the epsilon4 allele of APOE and density and spread of plaques (SP) and tangles (NFT). CSF levels of Abeta(1-42), T-tau and P-tau(181P) were determined in 50 Alzheimer's disease patients using commercially available single parameter ELISA kits (INNOTEST(R)). 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 epsilon4 carriers (n = 21) and non-carriers (n = 29) (P > 0.05 for all comparisons). No significant correlations between the number of epsilon4 alleles (0, 1 or 2) and CSF levels of Abeta(1-42) (Spearman Rank Order: r = -0.057, P = 0.695), T-tau (r = 0.104, P = 0.472) and P-tau(181P) (r = 0.062, P = 0.668) were found. Braak's SP (Abeta(1-42): r = -0.155, P = 0.280; T-tau: r = -0.044, P = 0.763; P-tau(181P): r = -0.010, P = 0.947) and NFT (Abeta(1-42): r = -0.145, P = 0.315; T-tau: r = 0.117, P = 0.415; P-tau(181P): r = 0.150, P = 0.296) stages were not significantly correlated with CSF biomarker levels. In conclusion, CSF levels of Abeta(1-42), T-tau and P-tau(181P) were not associated with epsilon4, 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.
authors.affiliation: Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Antwerpen, Belgium.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brouwers
authors.forename: Sally
authors.initials: S
authors.lastname: Serneels
authors.forename: Evelyn
authors.initials: E
authors.lastname: De Leenheir
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Eugeen
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins