MedNexus
2020年 · 第100卷第35期
MedNexus
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Alzheimer's disease (AD) is the most common type of senile dementia, characterized by progressive neurological degeneration, and is an important cause of disability in the elderly[
The list of members of the expert group for the formulation of this consensus:
Alzheimer's disease (AD) has become one of the diseases that seriously endanger the health and quality of life of the elderly worldwide. However, there is no effective drug that can cure AD at present. The main reason for the failure of previous AD drugs in clinical trials may be that the subject's disease course is already at a late stage. If there are biomarkers that can predict AD in the early onset or even asymptomatic stage of AD patients, and then intervene in patients, the appearance of clinical symptoms of patients may be delayed, thus improving the current treatment dilemma of AD. To this end, the research team recruited subjects from a longitudinal study 10 years ago to explore biomarkers for early diagnosis of AD. A total of 739 subjects were enrolled and divided into two stages: discovery and validation of exosomal synaptic proteins and establishment and validation of predictive models. During the discovery and validation stages, exosomal synaptic growth-associated protein 43 (GAP43), Neurogranin, synaptosome-associated protein 25 (SNAP25) and Synaptotagmin 1 in AD and mild cognitive impairment (MCI) subjects were significantly lower than those in the control group (P<0.001), exosomal biomarker levels correlated with levels in CSF (R2=0.54~0.70)。 In order to further verify the predictive ability of these exosomal synaptic proteins on the asymptomatic phase of AD, the team established a predictive model for the population of subjects with normal cognitive function 5 to 7 years ago and now developed AD, and predicted the incidence of this population. Subsequently, the predictive model was further validated in the familial AD cohort. Through ROC curve and ridge regression analysis, exosomal biomarkers had high efficacy to reflect brain pathological changes (AUCs =0.87-0.89), and could detect AD 5-7 years before cognitive impairment.
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