Abstract
BackgroundProgressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.MethodsWe analyzed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after 2 years [<4 points (N = 11) and ≥4 points (N = 8)]. The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N = 53) with mild AD using RT-qPCR.ResultsIn the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r = −0.28; p = 0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after 2 years (p = 0.049).ConclusionLower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after 2 years of follow-up.
Highlights
Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that gradually destroys memory and other thinking skills and, eventually, leads to complete dependency in daily life activities (Long and Holtzman, 2019)
We aimed to detect and validate baseline circulating miRNAs that can be associated with the rate of cognitive decline in patients with AD after 2 years of followup
This study was designed to detect the association of miRNAs with the rate of cognitive decline measured by the Mini-Mental State Examination (MMSE) in patients with mild AD using a hypothesis-free approach
Summary
Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that gradually destroys memory and other thinking skills and, eventually, leads to complete dependency in daily life activities (Long and Holtzman, 2019). Extracellular amyloid plaques (accumulation of amyloidβ (Aβ) protein) and intracellular neurofibrillary tangles (aggregations of hyperphosphorylated tau protein, P-tau) are two main pathological hallmarks of AD Both of these pathological characteristics are considered specific to AD, none of them have demonstrated a good correlation with the clinical symptoms (Jack et al, 2018). The measurement of some proteins released in CSF, such as tau and neurofilament light chain, can be used to assess neurodegeneration and has shown a good correlation with cognitive decline (Jack et al, 2018; Preische et al, 2019). They are not specific to neuronal damage due to AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD
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