Evidence map›Paper›PMID 41699702›Full record

ArticleFluids and barriers of the CNS2026

Mutations associated with Alzheimer's disease and aged serum synergistically elicit blood-brain barrier dysfunction in a tissue-engineered model.

Tracy D Chung, Lily Liang, Linus Wang, Elizabeth G Kim, Sukriti Gupta, Ikshu Pandey, Peter C Searson

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In one paragraph

Article in Fluids and barriers of the CNS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Tracy D ChungInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Lily LiangInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Linus WangInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Elizabeth G KimInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Sukriti GuptaInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Ikshu PandeyInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Peter C SearsonInstitute for Nanobiotechnology, 107 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA. searson@jhu.edu.

Funding

Reverse engineering zonation-specific and age-specific iPSC-derived cerebrovascular models based on transcriptomic profiling of the human brainR33HL154252 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI HEIMAN, MYRIAM, SEARSON, PETER C · 2023 to 2025
$1.3M
NIH HHS R33HL154252
6 · The paper itself

Abstract

backgroundAlzheimer’s disease is heterogeneous with a wide range of etiological subtypes derived from multiple risk factors. Many of these risk factors are either directly or indirectly related to stresses that act on the blood-bran barrier. Deconvoluting the influence of these stresses on blood-brain barrier function is important in understanding disease mechanisms and subtypes.

methodsWe used a tissue-engineered model with stem-cell derived brain microvascular endothelial cells (iBMECs) to assess the combined influence of cell-intrinsic mutations associated with Alzheimer’s disease (APP(Swe) and PSEN1(M146V)) and the systemic influence of aged blood components by perfusion with aged or young human serum. Blood-brain barrier dysfunction was assessed by transcriptomic analysis of iBMECs, functional measurements, and immunofluorescence imaging.

resultsMutations alone had no impact on permeability of small or large molecular weight solutes. Both aged serum and young serum resulted in increases in permeability of Lucifer yellow and 10 kDa dextran in APP and PSEN microvessels. The combination of aged serum and APP/PSEN1 mutations also resulted in an increase in adhesion of THP-1 neutrophil-like cells, and an increase in sprout length in an angiogenesis assay.

conclusionsThese results suggest that mutations associated with AD harbored by BMECs and age-related changes in plasma protein composition do not individually result in significant BBB dysfunction. However, the combinatorial effect of these stresses can induce modes of BBB dysfunction.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-Protein PrecursorBlood-Brain BarrierEndothelial CellsMutationPresenilin-1SerumCells, CulturedHumansMicrovesselsTissue EngineeringAmyloid beta-Protein PrecursorAPP protein, humanPresenilin-1PSEN1 protein, humanAgingAlzheimer’s diseaseBlood-brain barrierCerebrovasculature

Identifiers

PMID41699702
PMCPMC13011675

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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 OpenQuestion graph.