The A beta 1-42/A beta 1-40 ratio in CSF is more strongly associated to tau markers and clinical progression than A beta 1-42 alone
Por:
Delaby, C, Estelles, T, Zhu, NU, Arranz, J, Barroeta, I, Carmona-Iragui, M, Illan-Gala, I, Santos-Santos, MA, Altuna, M, Sala, I, Sanchez-Saudinos, MB, Videla, L, Valldeneu, S, Subirana, A, Tondo, M, Blanco-Vaca, F, Lehmann, S, Belbin, O, Blesa, R, Fortea, J, Lleo, A, Alcolea, D
Publicada:
1 feb 2022
Resumen:
Background: Cerebrospinal fluid (CSF) A beta 1-42 levels and the A beta 1-42/A beta 1-40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes.
Aims: To compare A beta 1-42 and the A beta 1-42/A beta 1-40 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 A beta 1-42 and A beta 1-42/A beta 1-40. 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 A beta 1-42 and A beta 1-42/A beta 1-40 was 78.3%. The A beta 1-42/A beta 1-40 ratio showed a stronger correlation with tTau and pTau181 than A beta 1-42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low A beta 1-42/A beta 1-40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for A beta 1-42. The results were consistent across stages, diagnostic categories, and use of different cutoffs.
Conclusion: Although A beta 1-42 and A beta 1-42/A beta 1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the A beta 1-42/A beta 1-40 ratio in clinical laboratories in the context of AD.
Filiaciones:
Delaby, C:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
Univ Montpellier, CHU Montpellier, INSERM, IRMB,INM,Lab Biochimie Proteomique clin, Montpellier, France
Estelles, T:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Zhu, NU:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Arranz, J:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Barroeta, I:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Carmona-Iragui, M:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Illan-Gala, I:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Santos-Santos, MA:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Altuna, M:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Sala, I:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Sanchez-Saudinos, MB:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Videla, L:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Ctr Med Down, Fdn Catalana Sindrome Down, Barcelona, Spain
Valldeneu, S:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Subirana, A:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Tondo, M:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Serv Bioquim, Barcelona, Spain
Unv Autonoma Barcelona, Serv Bioquim Biol Mol, Barcelona, Spain
Ctr Invest Biomed Red Diabet Enfermedades, Madrid, Spain
Blanco-Vaca, F:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Serv Bioquim, Barcelona, Spain
Unv Autonoma Barcelona, Serv Bioquim Biol Mol, Barcelona, Spain
Ctr Invest Biomed Red Diabet Enfermedades, Madrid, Spain
Lehmann, S:
Univ Montpellier, CHU Montpellier, INSERM, IRMB,INM,Lab Biochimie Proteomique clin, Montpellier, France
Belbin, O:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Blesa, R:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Hosp Sant Pau, Inst dInvest Biomed Sant Pau, Dept Neurol,Sant Pau Memory Unit, Sant Antoni Maria Claret 167, Barcelona 08025, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
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