Evidence map›Paper›PMID 40909593›Full record

ArticlebioRxiv : the preprint server for biology2025

Angiopoietin signalling is a central axis of amyloid-driven vascular dysfunction in Alzheimer's disease.

Matthias Flotho, Andrew Yang, Fabian Kern, Simon Graf, Ian Ferenc Diks, Heather Shin, Kristy A Zera, Daniela Berdnik, Maayan R Agam, Divya Channappa and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

19 authors.

Matthias FlothoClinical Bioinformatics, Saarland University, 66123, Saarbrücken, Germany.ORCID 0009-0006-4374-0801
Andrew YangDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Fabian KernClinical Bioinformatics, Saarland University, 66123, Saarbrücken, Germany.ORCID 0000-0002-8223-3750
Simon GrafClinical Bioinformatics, Saarland University, 66123, Saarbrücken, Germany.
Ian Ferenc DiksClinical Bioinformatics, Saarland University, 66123, Saarbrücken, Germany.
Heather ShinDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Kristy A ZeraDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Daniela BerdnikDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Maayan R AgamDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Divya ChannappaDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Sophia M ShiWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Malia Alexandra BelnapDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Epiphani C SimmonsDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Karen BradshawDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Friederike GrandkeClinical Bioinformatics, Saarland University, 66123, Saarbrücken, Germany.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Marion BuckwalterDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Andreas KellerClinical Bioinformatics, Saarland University, 66123, Saarbrücken, Germany.
Tony Wyss-CorayDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-5893-0831

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Training Program in Basic NeuroscienceT32MH020016 · NIMH · STANFORD UNIVERSITY · PI Justin L Gardner, Merritt C Maduke · 1997 to 2026
$16.2M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIMH NIH HHS T32 MH020016
6 · The paper itself

Abstract

The neurovascular unit is critical for brain health, and its dysfunction has been linked to Alzheimer's disease (AD). However, a cell-type-resolved understanding of how diverse vascular cells become dysfunctional and contribute to disease has been missing. Here, we applied Vessel Isolation and Nuclei Extraction for Sequencing (VINE-seq) to build a comprehensive transcriptomic atlas from 101 individuals along AD progression. Our analysis of over 842,646 parenchymal and vascular nuclei reveals that vascular dysfunction in AD is driven by transcriptional changes rather than shifts in cell proportions, with brain endothelial cells (BECs) and smooth muscle cells (SMCs) most affected. Strikingly, these molecular signatures emerge early at the mild cognitive impairment (MCI) stage, implicating vascular dysfunction early in AD pathogenesis. Stratifying by pathology reveals distinct vascular responses to β-amyloid and tau: β-amyloid burden primarily perturbs BECs and SMCs, while tau pathology predominantly impacts glial cells. We identify dysregulated angiopoietin signaling across multiple vascular cell types as a key axis, with antagonistic ANGPT2 in vascular cells and ANGPT1 in astrocytes becoming progressively dysregulated with AD. Together, this work provides a foundational resource that reveals early and pathology-specific pathways of vascular dysfunction in AD.

Identifiers

PMID40909593
PMCPMC12407677

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.