No association of CSF biomarkers with APOEε4, plaque and tangle burden in definite Alzheimer's disease

The CSF biomarkers b-amyloid peptide (Ab1^42), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) were determined in autopsy-confirmed Alzheimer’s disease patients in order to study possible associations with the e4 allele of APOE and density and spread of plaques (SP) and tangles (NFT). CSF levels of Ab1^42, T-tau and P-tau181P were determined in 50 Alzheimer’s disease patients using commercially available single parameter ELISA kits (INNOTEST ). 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 e4 carriers (n^21) and non-carriers (n^29) (P`0.05 for all comparisons). No significant correlations between the number of e 4a lleles (0, 1 or 2) and CSF levels of Ab1^42 (Spearman Rank Order: r^20.057, P^0.695), T-tau (r^0.104, P^0.472) and P-tau181P (r^0.062, P^0.668) were found. Braak’s SP (Ab1^42: r^20.155, P ¼ 0.280; T-tau: r^20.044, P ¼ 0.763; P-tau181P: r^20.010, P^0.947) and NFT (Ab1^42: r^20.145, P^0.315; T-tau: r^0.117, P^0.415; P-tau181P: r^0.150, P^0.296) stages were not significantly correlated with CSF biomarker levels. In conclusion, CSF levels of Ab1^42 ,T -tau and P-tau 181P were not associated with e4, 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.