期刊
ALZHEIMERS & DEMENTIA
卷 17, 期 1, 页码 49-60出版社
WILEY
DOI: 10.1002/alz.12166
关键词
Alzheimer's disease; biomarker; diagnosis; exosome; prediction; synaptic protein
资金
- National Natural Science Foundation of China [81530036]
- National Key Scientific Instrument and Equipment Development Project [31627803]
- Mission Program of Beijing Municipal Administration of Hospitals [SML20150801]
- Beijing Municipal Science& Technology Commission [Z161100000216137]
- Innovation Base Training and Development Special Program [Z171100002217007]
- Joint Initiative on Alzheimer's Disease and Related Disorders [81261120571, 81870825]
- Beijing Municipal Natural Science Foundation [7202061]
This study showed that exosomal GAP43, neurogranin, SNAP25, and synaptotagmin 1 serve as effective biomarkers for predicting AD 5 to 7 years before cognitive impairment.
Introduction: Exosomes are an emerging candidate for biomarkers of Alzheimer's disease (AD). This study investigated whether exosomal synaptic proteins can predict AD at the asymptomatic stage. Methods: We conducted a two-stage-sectional study (discovery stage: AD, 28; amnestic mild cognitive impairment [aMCI], 25; controls, 29; validation stage: AD, 73; aMCI, 71; controls, 72), a study including preclinical AD (160) and controls (160), and a confirmation study in familial AD (mutation carriers: 59; non-mutation carriers: 62). Results: The concentrations of growth associated protein 43 (GAP43), neurogranin, synaptosome associated protein 25 (SNAP25), and synaptotagmin 1 were lower in AD than in controls (P<.001). Exosomal biomarker levels were correlated with those in cerebrospinal fluid (R2 = 0.54-0.70). The combination of exosomal biomarkers detected AD 5 to 7 years before cognitive impairment (area under the curve = 0.870.89). Discussion: This study revealed that exosomal GAP43, neurogranin, SNAP25, and synaptotagmin 1 act as effective biomarkers for prediction of AD 5 to 7 years before cognitive impairment.
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