Evidence map›Paper›PMID 33440141›Full record

ArticleCell reports2021

Familial Alzheimer's Disease Mutations in PSEN1 Lead to Premature Human Stem Cell Neurogenesis.

Charles Arber, Christopher Lovejoy, Lachlan Harris, Nanet Willumsen, Argyro Alatza, Jackie M Casey, Georgie Lines, Caoimhe Kerins, Anika K Mueller, Henrik Zetterberg and 5 more

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

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% 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

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Pooled it
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  8. Biochemistry and biophysics reports · 2026
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16 more citing papers are in PubMed but not listed here.

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

15 authors at 5 institutions in 2 countries.

Charles ArberDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK. Electronic address: c.arber@ucl.ac.uk.
Christopher LovejoyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Lachlan HarrisNeural Stem Cell Biology Laboratory, The Francis Crick Institute, London, UK.
Nanet WillumsenDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London, UK.
Argyro AlatzaDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Jackie M CaseyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Georgie LinesDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Caoimhe KerinsDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Anika K MuellerDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Henrik ZetterbergDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, UK.
John HardyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
Natalie S RyanDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
Nick C FoxDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
Tammaryn LashleyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London, UK.
Selina WrayDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK. Electronic address: selina.wray@ucl.ac.uk.
National Hospital for Neurology and Neurosurgery · GBUK Dementia Research Institute · GBMRC Prion Unit · GBSahlgrenska University Hospital · SEThe Francis Crick Institute · GB

Funding

EPA EP-C-18-008Medical Research Council G0900421Medical Research Council MC_U12266BMedical Research Council MR/M02492X/1
6 · The paper itself

Abstract

Mutations in presenilin 1 (PSEN1) or presenilin 2 (PSEN2), the catalytic subunit of γ-secretase, cause familial Alzheimer's disease (fAD). We hypothesized that mutations in PSEN1 reduce Notch signaling and alter neurogenesis. Expression data from developmental and adult neurogenesis show relative enrichment of Notch and γ-secretase expression in stem cells, whereas expression of APP and β-secretase is enriched in neurons. We observe premature neurogenesis in fAD iPSCs harboring PSEN1 mutations using two orthogonal systems: cortical differentiation in 2D and cerebral organoid generation in 3D. This is partly driven by reduced Notch signaling. We extend these studies to adult hippocampal neurogenesis in mutation-confirmed postmortem tissue. fAD cases show mutation-specific effects and a trend toward reduced abundance of newborn neurons, supporting a premature aging phenotype. Altogether, these results support altered neurogenesis as a result of fAD mutations and suggest that neural stem cell biology is affected in aging and disease.

Indexed as

MutationAlzheimer DiseaseAmyloid Precursor Protein SecretasesCells, CulturedHumansInduced Pluripotent Stem CellsNeural Stem CellsNeurogenesisPresenilin-1Receptors, NotchAmyloid Precursor Protein SecretasesPresenilin-1PSEN1 protein, humanReceptors, NotchAlzheimer’s diseasehippocampusiPSCneurogenesisNOTCHorganoidPSEN1γ-secretase

Identifiers

PMID33440141
PMCPMC7809623
OpenAlexW3121043932

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.