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Blood neuro‐exosomal synaptic proteins predict Alzheimer's disease at the asymptomatic stage
Author(s) -
Jia Longfei,
Zhu Min,
Kong Chaojun,
Pang Yana,
Zhang Heng,
Qiu Qiongqiong,
Wei Cuibai,
Tang Yi,
Wang Qi,
Li Ying,
Li Tingting,
Li Fangyu,
Wang Qigeng,
Li Yan,
Wei Yiping,
Jia Jianping
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12166
Subject(s) - neurogranin , biomarker , synaptotagmin 1 , medicine , oncology , exosome , stage (stratigraphy) , asymptomatic , neuropathology , neuroscience , disease , microvesicles , psychology , biology , synaptic vesicle , genetics , gene , microrna , paleontology , vesicle , phosphorylation , protein kinase c , membrane
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 (R 2 = 0.54–0.70). The combination of exosomal biomarkers detected AD 5 to 7 years before cognitive impairment (area under the curve = 0.87–0.89). 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.