Higher Level of Mismatch in APOEε4 Carriers for Amyloid-Beta Peptide Alzheimer's Disease Biomarkers in Cerebrospinal Fluid.

Cerebrospinal fluid (CSF) biomarkers are widely used in the diagnosis of dementia. Even though there is a causal correlation between apolipoprotein E ( APOE) genotype and amyloid-beta (Aβ), the determination of APOE is currently not supported by national or international guidelines. We compared parallel measured CSF biomarkers of two independent laboratories from 126 patients who underwent clinical dementia diagnostics regarding the APOE genotype. APOE ε4 reduces Aβ1-42 (Aβ ₄₂ ) and Aβ ₄₂ to Aβ 1-40 ratio (Aβ _42/40 ) but not total Tau or phospho-181 Tau CSF levels. Higher discordance rates were observed for Aβ ₄₂ and subsequently for Aβ _42/40 in APOE ε4 carriers compared with noncarriers, and the correlation between the two laboratories was significantly lower for Aβ ₄₂ in APOE ε4 positive patients compared with patients without APOE ε4. These observations demonstrate that the evaluation of CSF Aβ biomarkers needs to be interpreted carefully in the clinical context. Different immunoassays, disparate cutoff values, and APOE should be respected.