Evidence mapPaperPMID 42368021Full record

ArticlebioRxiv : the preprint server for biology2026

MicroRNA-181 influences Alzheimer's risk by regulating neprilysin and microtubule-associated tau pathways, offering a novel target.

Ruizhi Wang, Bryan Maloney, Kwangsik Nho, John S Beck, Scott E Counts, Debomoy K Lahiri

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ruizhi WangLaboratory of Molecular Neurogenetics, Departments of Psychiatry, Stark Neuroscience Research Institute, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Bryan MaloneyLaboratory of Molecular Neurogenetics, Departments of Psychiatry, Stark Neuroscience Research Institute, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0003-2364-9649
Kwangsik NhoDepartment of Radiology & Imaging Sciences, Stark Neuroscience Research Institute, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-7624-3872
John S BeckDepartments of Translational Neuroscience and Family Medicine, Michigan State University, Grand Rapids, MI, USA.
Scott E CountsDepartments of Translational Neuroscience and Family Medicine, Michigan State University, Grand Rapids, MI, USA.ORCID 0000-0003-2851-9763
Debomoy K LahiriLaboratory of Molecular Neurogenetics, Departments of Psychiatry, Stark Neuroscience Research Institute, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-1664-5933

Funding

Alzheimer's Disease Neuroimaging InitiativeU01AG024904 · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · 2004 to 2005
$21.3M
TAU, AB, SYNUCLEIN AND NITRATIVE/OXIDATIVE DAMAGE IN MCIP01AG014449 · UNIVERSITY OF PITTSBURGH · 1997 to 2005
$7.8M
Research Education ComponentP30AG072976 · INDIANA UNIVERSITY INDIANAPOLIS · 2025 to 2025
$2.9M
Brain protein alteration by vascular overexpressed miRNA (BravomiR)R21AG076202 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI DEBOMOY K LAHIRI · 2022 to 2022
$435k
Alzheimer's disease-linked microRNA Exploration of UTR Polymorphisms (AdmiRE-UP)R21AG074539 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI DEBOMOY K LAHIRI · 2022 to 2022
$435k
NIA NIH HHS P01 AG014449NIA NIH HHS P30 AG072976NIA NIH HHS R21 AG056007NIA NIH HHS R21 AG074539NIA NIH HHS R21 AG076202NIA NIH HHS R56 AG051086NIA NIH HHS R56 AG072810NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide plaques and neurofibrillary tangles from hyperphosphorylated tau, though factors linking amyloid and tau pathology remain unclear. We investigated whether microRNA-181d-5p (miR-181d) associates with AD-related brain changes and regulates neprilysin and tau. Modeling miR-181d across individuals with no cognitive impairment, mild cognitive impairment, and AD revealed region- and sex-specific associations. Higher miR-181d levels associated with greater AD probability in the temporal lobe and cerebellum, and lower probability in the posterior cingulate cortex of males; miR-181c attenuated these probabilities. SNPs near MIR181 associated with altered entorhinal cortical thickness. In cellular models, miR-181 reduced neprilysin 3'-UTR activity, mRNA, protein, and enzymatic activity, while increasing tau mRNA and protein. Neprilysin diminution impairs Aβ clearance and elevates tau, contributing to AD. RNA sequencing identified miR-181d-responsive neurodegenerative pathways. These findings identify miR-181 as a regulator of AD-relevant amyloid and tau pathways, providing novel targets.

Indexed as

Agingamyloiddementiagenetic variantsmicroRNAneprilysinSNPstauUTR

Identifiers

PMID42368021
PMCPMC13307934

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.