Abstract
Alzheimer’s disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595–2.474), total-tau (SMD = 1.224, 95% CI: 0.534–1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795–4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder [1]
The current major challenge in early AD diagnosis is the lack of reliable biomarkers, which serve as measurable indicators of the biological state or pathological condition [5]
All the studies were published between 2015 and 2021. These studies were conducted in regions including the USA, Italy, Spain, Sweden, China, Korea, and Canada
Summary
The prevalence of AD in people over the age of 65 years is approximately 10%, and increases to. 32% in people aged 85 years, showing increasing prevalence with age [2]. The clinical diagnosis of AD is conventionally done after neuropsychological tests and exclusion of other age-related types of dementia. Cardinal progressive symptoms can support the clinical diagnosis, a definitive diagnosis can be made only on the postmortem examination of the brain, wherein the brain must contain sufficient amyloid plaques and neurofibrillary tangles indicative of the disease [3,4]. The current major challenge in early AD diagnosis is the lack of reliable biomarkers, which serve as measurable indicators of the biological state or pathological condition [5]. The search for AD diagnostic targets in patients is increasing in parallel to the increasing understanding
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