Brain Advance Access originally published online on June 22, 2007
Brain 2007 130(9):2320-2326; doi:10.1093/brain/awm136
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No association of CSF biomarkers with APOE
4, plaque and tangle burden in definite Alzheimer's disease
1Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), 2Reference Centre for Biological Markers of Memory Disorders, Laboratory of Neurochemistry and Behavior, 3Laboratory of Neurogenetics, 4Laboratory of Neurobiology and 5Biobank, Institute Born-Bunge, 6University of Antwerp, Antwerpen, Belgium, 7Department of Nursing Sciences, Faculty of Medicine, University of Antwerp, Antwerpen, Belgium, 8Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, 9Department of Neurology, University Hospital of Antwerp, Antwerpen, Belgium and 10Innogenetics NV, Gent, Belgium
Correspondence to: Prof. Dr P.P. De Deyn, Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, BE-2610 Antwerp, Belgium E-mail: peter.dedeyn{at}ua.ac.be.
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 
4 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 4 carriers (n = 21) and non-carriers (n = 29) (P > 0.05 for all comparisons). No significant correlations between the number of 4 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 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.
Key Words: dementia; Alzheimer's disease; biomarkers; CSF; APOE
Abbreviations: Aβ1–42, β-amyloid peptide; AD, Alzheimer's disease; DLB, dementia with Lewy bodies; MCI, mild cognitive impairment; NFT, neurofibrillary tangle; P-tau, hyperphosphorylated tau; SP, senile plaque; T-tau, total tau protein
Received December 12, 2006. Revised May 12, 2007. Accepted May 18, 2007.
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