Abstract
The rate of progression from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) is estimated at >10% per year, reaching up to 80–90% after 6 years. MCI is considered an indicator of early-stage AD. In this context, the diagnostic screening of MCI is crucial for detecting individuals at high risk of AD before they progress and manifest further severe symptoms. Typically, MCI has been determined using neuropsychological assessment tools such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental Status Examination (MMSE). Unfortunately, other diagnostic methods are not available or are unable to identify MCI in its early stages. Therefore, identifying new biomarkers for MCI diagnosis and prognosis is a significant challenge. In this framework, miRNAs in serum, plasma, and other body fluids have emerged as a promising source of biomarkers for MCI and AD-related cognitive impairments. Interestingly, miRNAs can regulate several signaling pathways via multiple and diverse targets in response to pathophysiological stimuli. This systematic review aims to describe the current state of the art regarding AD-related target genes modulated by differentially expressed miRNAs in peripheral fluids samples in MCI subjects to identify potential miRNA biomarkers in the early stages of AD. We found 30 articles that described five miRNA expression profiles from peripheral fluid in MCI subjects, showing possible candidates for miRNA biomarkers that may be followed up as fluid biomarkers or therapeutic targets of early-stage AD. However, additional research is needed to validate these miRNAs and characterize the precise neuropathological mechanisms.
Highlights
Diagnostic Criteria in MCIDiagnostic criteria for Mild Cognitive Impairment (MCI) have changed over time (Petersen, 2004; Winblad et al, 2004; Sachdev et al, 2015; Alzheimer’s Association, 2018)
Within the clinical criteria used in the 30 selected articles, 11 (36.6%) of them used the criteria established by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA), 9 (30%) papers applied the Petersen’s criteria
MiRNAs have become promising alternatives because (i) miRNAs can be detected from plasma, urine, saliva, cerebrospinal fluid (CSF), extracellular fluid, and tissues, (ii) cell-free miRNA are stable in blood samples (Tribolet et al, 2020), (iii) evidence indicates that miRNA expression patterns reflect some aberrant conditions, and sometimes, it shows a time-progression response (Keller et al, 2014), and (iv) miRNAs can be detected with qRT-PCR with no considerable time-consuming protocols and economic considerations
Summary
Diagnostic Criteria in MCIDiagnostic criteria for Mild Cognitive Impairment (MCI) have changed over time (Petersen, 2004; Winblad et al, 2004; Sachdev et al, 2015; Alzheimer’s Association, 2018). The diagnosis of MCI depends on which cognitive and functional tests are used (Albert et al, 2011), these include the Mini-Mental Status Examination (MMSE; Arevalo-Rodriguez et al, 2021) or the Montreal Cognitive Assessment (MoCA; Nasreddine et al, 2005; Albert et al, 2011; Ciesielska et al, 2016). Other cognitive assessments, including the MMSE and the Dementia Rating Scale (DRS), are not recommended as screening tools for MCI because of their specificity and sensitivity (Espino et al, 2001; Matallana et al, 2011). MoCA is currently more sensitive to diagnosing MCI than MMSE (Langa and Levine, 2014; Ciesielska et al, 2016)
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