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Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease

2015; Lippincott Williams & Wilkins; Volume: 85; Issue: 7 Linguagem: Inglês

10.1212/wnl.0000000000001859

1526-632X

Daniel Alcolea, Pablo Martínez‐Lage, Pascual Sánchez‐Juan, Javier Olazarán, Carmen Antúnez, Andrea Izagirre, M. Ecay, Ainara Estanga, Montserrat Clerigué, M.C. Guisasola, Domingo Sánchez Ruíz, Juan Marín, Miguel Calero, Rafael Blesa, Jordi Clarimón, María Carmona‐Iragui, Estrella Morenas‐Rodríguez, Eloy Rodríguez‐Rodríguez, José Luis Vázquez Higuera, Juan Fortea, Alberto Lleó,

Tryptophan and brain disorders

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–Alzheimer9s 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.