Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease

Daniel Alcolea, Pablo Martínez-Lage, Pascual Sánchez-Juan, Javier Olazarán, Carmen Antúnez, Andrea Izagirre, Mirian Ecay-Torres, Ainara Estanga, Montserrat Clerigué, Maria Concepción Guisasola, Domingo Sánchez Ruiz, Juan Marín Muñoz, Miguel Calero, Rafael Blesa, Jordi Clarimón, María Carmona-Iragui, Estrella Morenas-Rodríguez, Eloy Rodríguez-Rodríguez, José Luis Vázquez Higuera, Juan ForteaAlberto Lleó

Research output: Contribution to journalArticleResearchpeer-review

121 Citations (Scopus)


© 2015 American Academy of Neurology. Objective: To investigate CSF markers involved in amyloid precursor protein processing, neuronal damage, and neuroinflammation in the preclinical stages of Alzheimer disease (AD) and participants with suspected non-Alzheimer pathology (SNAP). Methods: We collected CSF from 266 cognitively normal volunteers participating in a cross-sectional multicenter study (the SIGNAL study) to investigate markers involved in amyloid precursor protein processing (Aβ42, sAPPβ, β-secretase activity), neuronal damage (total-tau [t-tau], phospho-tau [p-tau]), and neuroinflammation (YKL-40). We analyzed the relationship among biomarkers, clinical variables, and the APOE genotype, and compared biomarker levels across the preclinical stages of the National Institute on Aging-Alzheimer's Association classification: stage 0, 1, 2, 3, and SNAP. Results: The median age in the whole cohort was 58.8 years (range 39.8-81.6). Participants in stages 2-3 and SNAP had higher levels of YKL-40 than those in stages 0 and 1. Participants with SNAP had higher levels of sAPPβ than participants in stage 0 and 1. No differences were found between stages 0, 1, and 2-3 in sAPPβ and β-secretase activity in CSF. Age correlated with t-tau, p-tau, and YKL-40. It also correlated with Aβ42, but only in APOE ε4 carriers. Aβ42 correlated positively with t-tau, sAPPβ, and YKL-40 in participants with normal Aβ42. Conclusions: Our findings suggest that inflammation in the CNS increases in normal aging and is intimately related to markers of neurodegeneration in the preclinical stages of AD and SNAP. sAPPβ and β-secretase activity are not useful diagnostic or staging markers in preclinical AD.
Original languageEnglish
Pages (from-to)626-633
Issue number7
Publication statusPublished - 1 Jan 2015


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