Evidence map›Paper›PMID 40316675›Full record

ArticleMolecular psychiatry2025

Alzheimer's disease patient brain extracts induce multiple pathologies in novel vascularized neuroimmune organoids for disease modeling and drug discovery.

Yanru Ji, Xiaoling Chen, Zhen Wang, Connor Joseph Meek, Jenna Lillie McLean, Yang Yang, Chongli Yuan, Jean-Christophe Rochet, Fei Liu, Ranjie Xu

Abstract read
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

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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

10 authors.

Yanru JiDepartment of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.
Xiaoling ChenPurdue Institute for Integrative Neuroscience (PIIN), Purdue University, West Lafayette, IN, 47907, USA.ORCID http://orcid.org/0000-0002-2271-1140
Zhen WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Connor Joseph MeekDepartment of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.
Jenna Lillie McLeanDepartment of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.
Yang YangPurdue Institute for Integrative Neuroscience (PIIN), Purdue University, West Lafayette, IN, 47907, USA.ORCID http://orcid.org/0000-0001-6417-3654
Chongli YuanPurdue Institute for Integrative Neuroscience (PIIN), Purdue University, West Lafayette, IN, 47907, USA.
Jean-Christophe RochetPurdue Institute for Integrative Neuroscience (PIIN), Purdue University, West Lafayette, IN, 47907, USA.
Fei LiuDepartment of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA.ORCID http://orcid.org/0000-0001-8601-4419
Ranjie XuDepartment of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA. xu1726@purdue.edu.ORCID http://orcid.org/0000-0001-9401-6430

Funding

Elucidate Gene-environmental interactions employed by Pb in promoting ADRD in aging brainsU01AG088662 · NIA · PURDUE UNIVERSITY · PI Ranjie Xu, Chongli Yuan · 2024 to 2026
$2.3M
Develop a human-mouse chimeric brain model for studying tau pathology in human neuron in vivoR21NS140907 · NINDS · PURDUE UNIVERSITY · PI XU, RANJIE · 2024 to 2025
$432k
NIA NIH HHS U01 AG088662NINDS NIH HHS R21 NS140907U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R21NS140907U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG088662
6 · The paper itself

Abstract

Alzheimer's Disease (AD) is the most common cause of dementia, afflicting 55 million individuals worldwide, with limited treatment available. Current AD models mainly focus on familial AD (fAD), which is due to genetic mutations. However, models for studying sporadic AD (sAD), which represents over 95% of AD cases without specific genetic mutations, are severely limited. Moreover, the fundamental species differences between humans and animals might significantly contribute to clinical failures for AD therapeutics that have shown success in animal models, highlighting the urgency to develop more translational human models for studying AD, particularly sAD. In this study, we developed a complex human pluripotent stem cell (hPSC)-based vascularized neuroimmune organoid model, which contains multiple cell types affected in human AD brains, including human neurons, microglia, astrocytes, and blood vessels. Importantly, we demonstrated that brain extracts from individuals with sAD can effectively induce multiple AD pathologies in organoids four weeks post-exposure, including amyloid beta (Aβ) plaque-like aggregates, tau tangle-like aggregates, neuroinflammation, elevated microglial synaptic pruning, synapse/neuronal loss, and impaired neural network activity. Proteomics analysis also revealed disrupted AD-related pathways in our vascularized AD neuroimmune organoids. Furthermore, after treatment with Lecanemab, an FDA-approved antibody drug targeting Aβ, AD brain extracts exposed organoids showed a significant reduction of amyloid burden, along with an elevated vascular inflammation response. Thus, the vascularized neuroimmune organoid model provides a unique opportunity to study AD, particularly sAD, under a pathophysiological relevant three-dimensional (3D) human cell environment. It also holds great promise to facilitate AD drug development, particularly for immunotherapies.

Indexed as

Alzheimer DiseaseBrainOrganoidsAmyloid beta-PeptidesDrug DiscoveryHumansMicrogliaNeuronsPlaque, AmyloidPluripotent Stem Cellstau ProteinsAmyloid beta-Peptidestau Proteins

Identifiers

PMID40316675
PMCPMC12436168

What Socratic holds

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LicenceCC BY
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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 Socratic graph.