Journal Article

No association of CSF biomarkers with APOE<b>ε</b>4, plaque and tangle burden in definite Alzheimer's disease

Sebastiaan Engelborghs, Kristel Sleegers, Patrick Cras, Nathalie Brouwers, Sally Serneels, Evelyn De Leenheir, Jean-Jacques Martin, Eugeen Vanmechelen, Christine Van Broeckhoven and Peter Paul De Deyn

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 9, pages 2320-2326
Published in print September 2007 | ISSN: 0006-8950
Published online June 2007 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awm136
No association of CSF biomarkers with APOEε4, plaque and tangle burden in definite Alzheimer's disease

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The CSF biomarkers β-amyloid peptide (Aβ1–42), 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 ε4 allele of APOE and density and spread of plaques (SP) and tangles (NFT).

CSF levels of Aβ1–42, 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 ε4 carriers (n= 21) and non-carriers (n= 29) (P> 0.05 for all comparisons). No significant correlations between the number of ε4 alleles (0, 1 or 2) and CSF levels of Aβ1–42 (Spearman Rank Order: r=0.057, 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 (Aβ1–42: r=0.155, P = 0.280; T-tau: r= −0.044, P = 0.763; P-tau181P: r= −0.010, P= 0.947) and NFT (Aβ1–42: r= −0.145, 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 Aβ1–42, T-tau and P-tau181P were not associated with ε4, 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.

Keywords: dementia; Alzheimer's disease; biomarkers; CSF; APOE

Journal Article.  4540 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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