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The preclinical diagnosis and clinical practice for Alzheimer’s disease (AD) based on liquid biopsy have made great progress in recent years. As liquid biopsy is a fast, low-cost, and easy way to get the phase of AD, continual efforts from intense multidisciplinary studies have been made to move the research tools to routine clinical diagnostics. On one hand, technological breakthroughs have brought new detection methods to the outputs of liquid biopsy to stratify AD cases, resulting in higher accuracy and efficiency of diagnosis. On the other hand, diversiform biofluid biomarkers derived from cerebrospinal fluid (CSF), blood, urine, Saliva, and exosome were screened out and biologically verified. As a result, more detailed knowledge about the molecular pathogenesis of AD was discovered and elucidated. However, to date, how to weigh the reports derived from liquid biopsy for preclinical AD diagnosis is an ongoing question. In this review, we briefly introduce liquid biopsy and the role it plays in research and clinical practice. Then, we summarize the established fluid-based assays of the current state for AD diagnostic such as ELISA, single-molecule array (Simoa), Immunoprecipitation–Mass Spectrometry (IP–MS), liquid chromatography–MS, immunomagnetic reduction (IMR), multimer detection system (MDS). In addition, we give an updated list of fluid biomarkers in the AD research field. Lastly, the current outstanding challenges and the feasibility to use a stand-alone biomarker in the joint diagnostic strategy are discussed.

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