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Amyloid β peptide ratio 42/40 but not Aβ42 correlates with phospho‐Tau in patients with low‐ and high‐CSF Aβ40 load

Neurochemical dementia diagnostics (NDD) can significantly improve the clinically based categorization of patients with early dementia disorders, and the cerebrospinal fluid (CSF) concentrations of amyloid β peptides ending at the amino acid position of 42 (Aβx‐42 and Aβ1‐42) are widely accepted biomarkers of Alzheimer’s disease (AD). However, in subjects with constitutively high‐ or low‐CSF concentrations of total Aβ peptides (tAβ), the NDD interpretation might lead to erroneous conclusions as these biomarkers seem to correlate better with the total Aβ load than with the pathological status of a given patient in such cases. In this multicenter study, we found significantly increased CSF concentrations of phosphorylated Tau (pTau181) and total Tau in the group of subjects with high CSF Aβx‐40 concentrations and decreased Aβx‐42/x‐40 concentration ratio compared with the group of subjects with low CSF Aβx‐40 and normal Aβ ratio (p < 0.001 in both cases). Furthermore, we observed significantly decreased Aβ ratio (p < 0.01) in the group of subjects with APOE ε4 allele compared with the group of subjects without this allele. Surprisingly, patients with low‐Aβx‐40 and the decreased Aβ ratio characterized with decreased pTau181 (p < 0.05), and unaltered total Tau compared with the subjects with high Aβx‐40 and the Aβ ratio in the normal range. We conclude that the amyloid β concentration ratio should replace the ‘raw’ concentrations of corresponding Aβ peptides to improve reliability of the neurochemical dementia diagnosis.