Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer’s disease

Abstract

Background The most common biomarkers of Alzheimer’s disease (AD) are amyloid β (Aβ) and tau, detected in cerebrospinal fluid (CSF) or with positron emission tomography imaging. However, these procedures are invasive and expensive, which hamper their availability to the general population. Here, we report a panel of microRNAs (miRNAs) in serum that can predict P-tau/Aβ42 in CSF and readily differentiate AD from other dementias, including vascular dementia (VaD), Parkinson disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). Methods RNA samples were extracted from the participant’s blood. P-tau/Aβ42 of CSF was examined for diagnostic purposes. A pilot study (controls, 21; AD, 23), followed by second (controls, 216; AD, 190) and third groups (controls, 153; AD, 151), is used to establish and verify a predictive model of P-tau/Aβ42 in CSF. The test is then applied to a fourth group of patients with different dementias (controls, 139; AD,155; amnestic mild cognitive impairment [aMCI], 55; VaD, 51; PDD, 53; bvFTD, 53; DLB, 52) to assess its diagnostic capacity. Results In the pilot study, 29 upregulated and 31 downregulated miRNAs in the AD group were found. In Dataset 2, these miRNAs were then included as independent variables in the linear regression model. A seven-microRNA panel (miR-139-3p, miR-143-3p, miR-146a-5p, miR-485-5p, miR-10a-5P, miR-26b-5p, and miR-451a-5p) accurately predicted values of P-tau/Aβ42 of CSF. In Datasets 3 and 4, by applying the predicted P-tau/Aβ42, the predictive model successfully differentiates AD from controls and VaD, PDD, bvFTD, and DLB. Conclusions This study suggests that the panel of microRNAs is a promising substitute for traditional measurement of P-tau/Aβ42 in CSF as an effective biomarker of AD.

miR-143-3p Inhibits Aberrant Tau Phosphorylation and Amyloidogenic Processing of APP by Directly Targeting DAPK1 in Alzheimer’s Disease

“…In this study, the hsa-miR-143-3p levels were found to be decreased in the hippocampus of individuals with AD compared with the controls. Consistent with these data, other studies showed that hsa-miR-143-3p was dramatically reduced in the serum of individuals with AD relative to the controls and provide a promising noninvasive biomarker for AD diagnosis [ 35 , 37 ]. In contrast, the hsa-miR-143-3p levels have been found to be increased in exosomes isolated from the serum of patients with AD compared with control subjects [ 34 ].…”

“…Our group recently showed that melatonin interacts with DAPK1 to inhibit protein expression, but a loss of melatonin might not be sufficient to augment the protein stabilization of DAPK1, which indicates that the expression of DAPK1 is modulated by multiple mechanisms, including miRNAs, in AD [ 14 , 21 ]. By employing a variety of miRNA online databases, we identified hsa-miR-143-3p as an attractive and novel biomarker for early AD diagnosis [ 34 , 35 , 36 , 37 ]. Through validation using dual-luciferase reporter assays, we provide the first demonstration showing that human DAPK1 is a direct target of hsa-miR-143-3p.…”

“…MicroRNA-143 (miR-143) is part of a bicistronic cluster composed of miR-143 and miR-145, which is located on chromosome 5 position 33 (5q33) in the human genome and has been implicated in the carcinogenesis [ 32 , 33 ]. Recent findings showing the diagnostic potential of hsa-miR-143-3p for AD have inspired many researchers [ 34 , 35 , 36 , 37 ]. However, the hsa-miR-143-3p levels in adult brains and the molecular mechanisms of hsa-miR-143-3p in AD pathogenesis remain unclear.…”

CSF α-Synuclein and Tau as Biomarkers for Dementia With Lewy Bodies

“…1). Among them, 35 studies4,6,7,12-43 related to tau (Supplemental Digital Content 1, which demonstrates characteristics of studies used for analysis of CSF tau levels in DLB, http://links.lww.com/WAD/A401), and 14 studies4-7,12,14,20,22,23,27,39,40,42,44 related to α-synuclein (Supplemental Digital Content 2, which demonstrates characteristics of studies used for analysis of CSF α-synuclein levels in DLB, http://links.lww.com/WAD/A402) were included, and 12 studies overlapped with each other.…”

microRNA pathological mechanisms between Parkinson's disease, Alzheimer's disease, glaucoma and macular degeneration

“…A panel of miRNAs including miR-143-3p is a promising substitute for the traditional measurement of p-tau/A β -42 in cerebrospinal fluid as an effective biomarker of AD (Ref. 95). Overexpression of miR-26a-5p suppressed tau phosphorylation and A β accumulation in the AD mice by targeting DYRK1A (Ref.…”