Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (11): 2381-2390.doi: 10.4103/1673-5374.335832

Previous Articles     Next Articles

Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer’s disease: a meta-analysis and systematic review

Wei-Lin Liu1, 2, #, Hua-Wei Lin1, #, Miao-Ran Lin3, Yan Yu3, Huan-Huan Liu1, Ya-Ling Dai3, Le-Wen Chen1, Wei-Wei Jia3, Xiao-Jun He1, Xiao-Ling Li3, Jing-Fang Zhu3, Xie-Hua Xue4, Jing Tao1, Li-Dian Chen1, *   

  1. 1Academy of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China; 2Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 3National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China; 4Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
  • Online:2022-11-15 Published:2022-04-21
  • Contact: Li-Dian Chen, PhD, cld@fjtcm.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China (Key Project), No. 82030123 (to LDC), the Science and Technology Platform Construction Project of Fujian Science and Technology Department, No. 2018Y2002 (to LDC).

PDF

1265

Abstract: Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer’s disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer’s disease, mild cognitive impairment, and Alzheimer’s disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer’s disease, mild cognitive impairment, and preclinical Alzheimer’s disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ1–42, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer’s disease, mild cognitive impairment, and Alzheimer’s disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer’s disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer’s disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).

Key words: Alzheimer’s disease, amyloid-β, biomarkers, blood, exosomes, extracellular vesicles, meta-analysis, mild cognitive impairment, systematic review, tau protein