Evidence map›Paper›PMID 38552634›Full record

ArticleStem cell reports2024

Conclusive demonstration of iatrogenic Alzheimer's disease transmission in a model of stem cell transplantation.

Chaahat S B Singh, Kelly Marie Johns, Suresh Kari, Lonna Munro, Angela Mathews, Franz Fenninger, Cheryl G Pfeifer, Wilfred A Jefferies

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
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

8 citing papers in PubMed, 11 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Chaahat S B SinghMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada.
Kelly Marie JohnsMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada.
Suresh KariMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada.
Lonna MunroMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada.
Angela MathewsMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada.
Franz FenningerMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada.
Cheryl G PfeiferMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada.
Wilfred A JefferiesMichael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, BC V6T 1Z4, Canada; Department of Urologic Sciences, University of British Columbia, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9 Canada. Electronic address: wilf@msl.ubc.ca.
University of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The risk of iatrogenic disease is often underestimated as a concern in contemporary medical procedures, encompassing tissue and organ transplantation, stem cell therapies, blood transfusions, and the administration of blood-derived products. In this context, despite the prevailing belief that Alzheimer's disease (AD) manifests primarily in familial and sporadic forms, our investigation reveals an unexpected transplantable variant of AD in a preclinical context, potentially indicating iatrogenic transmission in AD patients. Through adoptive transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into either APP-deficient knockout or normal recipient animals, we observed rapid development of AD pathological hallmarks. These pathological features were significantly accelerated and emerged within 6-9 months post transplantation and included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated β-amyloid levels, and cognitive impairment. Furthermore, our findings underscore the contribution of β-amyloid burden originating outside of the central nervous system to AD pathogenesis within the brain. We conclude that stem cell transplantation from donors harboring a pathogenic mutant allele can effectively transfer central nervous system diseases to healthy recipients, mirroring the pathogenesis observed in the donor. Consequently, our observations advocate for genomic sequencing of donor specimens prior to tissue, organ, or stem cell transplantation therapies, as well as blood transfusions and blood-derived product administration, to mitigate the risk of iatrogenic diseases.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalHumansIatrogenic DiseaseMiceMice, TransgenicStem Cell TransplantationAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAlzheimer’s diseaseblood transfusionCNS disordersiatrogenic diseasesmegakaryocytes derived amyloid betamouse behaviour analysisorgan transplantprion diseasesprotein misfoldingstem-cell transplant

Identifiers

PMID38552634
PMCPMC11096610
OpenAlexW4393255484

What OpenQuestion holds

Textmetadata
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.