Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease.
Neurology
; 85(7): 626-33, 2015 Aug 18.
Article
em En
| MEDLINE
| ID: mdl-26180139
ABSTRACT
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 (Aß42, sAPPß, ß-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 sAPPß than participants in stage 0 and 1. No differences were found between stages 0, 1, and 2-3 in sAPPß and ß-secretase activity in CSF. Age correlated with t-tau, p-tau, and YKL-40. It also correlated with Aß42, but only in APOE ε4 carriers. Aß42 correlated positively with t-tau, sAPPß, and YKL-40 in participants with normal Aß42.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. sAPPß and ß-secretase activity are not useful diagnostic or staging markers in preclinical AD.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Precursor de Proteína beta-Amiloide
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Proteínas tau
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Secretases da Proteína Precursora do Amiloide
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Adipocinas
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Doença de Alzheimer
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Sintomas Prodrômicos
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Lectinas
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prevalence_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article