Blood neuro‐exosomal synaptic proteins predict Alzheimer's disease at the asymptomatic stage

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 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.