The Aβ1–42/Aβ1–40 ratio in CSF is more strongly associated to tau markers and clinical progression than Aβ1–42 alone

• Published in: Alzheimer's research & therapy Vol. 14; no. 1; pp. 20 - 11
• Main Authors: Delaby, Constance, Estellés, Teresa, Zhu, Nuole, Arranz, Javier, Barroeta, Isabel, Carmona-Iragui, María, Illán-Gala, Ignacio, Santos-Santos, Miguel Ángel, Altuna, Miren, Sala, Isabel, Sánchez-Saudinós, M. Belén, Videla, Laura, Valldeneu, Sílvia, Subirana, Andrea, Tondo, Mireia, Blanco-Vaca, Francisco, Lehmann, Sylvain, Belbin, Olivia, Blesa, Rafael, Fortea, Juan, Lleó, Alberto, Alcolea, Daniel
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01.02.2022; BMC
• Subjects: Age; Agreements; Alzheimer Disease; Alzheimer Disease - cerebrospinal fluid; Alzheimer's disease; Amyloid; Amyloid beta-Peptides; Amyloid beta-Peptides - cerebrospinal fluid; Aβ1–40; Aβ1–42; Biomarkers; Biomarkers - cerebrospinal fluid; Biomedical and Life Sciences; Biomedicine; Cerebrospinal fluid; Cognitive ability; Cognitive science; Dementia; Demographics; Diagnostic tests; Geriatric Psychiatry; Geriatrics/Gerontology; Humans; Medical laboratories; Neurodegeneration; Neurology; Neuroscience; Neurosciences; Peptide Fragments; Peptide Fragments - cerebrospinal fluid; Quality control; Tau; tau Proteins; tau Proteins - cerebrospinal fluid; Biomarkers; Tau; Amyloid; Aβ1–40; Cerebrospinal fluid; Aβ1–42
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-022-00967-z

Background Cerebrospinal fluid (CSF) Aβ1–42 levels and the Aβ1–42/Aβ1–40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes. Aims To compare Aβ1–42 and the Aβ1–42/Aβ1–40 ratio in CSF in different neurodegenerative disorders and study their association with other biomarkers (tTau, pTau181, and NfL) and with cognitive and functional progression. Methods We included all participants from the Sant Pau Initiative on Neurodegeneration (SPIN) with CSF Aβ1–42 and Aβ1–42/Aβ1–40. Participants had diagnoses of Alzheimer’s disease (AD), dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal. We classified participants as “positive” or “negative” according to each marker. We compared CSF levels of tTau, pTau181, and NfL between concordant and discordant groups through ANCOVA and assessed differences in cognitive (MMSE, FCSRT) and functional (GDS, CDR-SOB) progression using Cox regression and linear-mixed models. Results In the 1791 participants, the agreement between Aβ1–42 and Aβ1–42/Aβ1–40 was 78.3%. The Aβ1–42/Aβ1–40 ratio showed a stronger correlation with tTau and pTau181 than Aβ1–42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low Aβ1–42/Aβ1–40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for Aβ1–42. The results were consistent across stages, diagnostic categories, and use of different cutoffs. Conclusion Although Aβ1–42 and Aβ1–42/Aβ1–40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the Aβ1–42/Aβ1–40 ratio in clinical laboratories in the context of AD.