Evidence map›Paper›PMID 37774681›Full record

ArticleCell2023

Early Alzheimer's disease pathology in human cortex involves transient cell states.

Vahid Gazestani, Tushar Kamath, Naeem M Nadaf, Antonios Dougalis, S J Burris, Brendan Rooney, Antti Junkkari, Charles Vanderburg, Anssi Pelkonen, Mireia Gomez-Budia and 14 more

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

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed
24.4field-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

147 citing papers in PubMed, 192 citations in OpenAlex.

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87 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 7 institutions in 2 countries.

Vahid GazestaniBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tushar KamathBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics and Harvard/MIT MD-PhD Program, Harvard University, Cambridge, MA 02139, USA.
Naeem M NadafBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Antonios DougalisA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
S J BurrisBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Brendan RooneyProgram in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Antti JunkkariInstitute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Charles VanderburgBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anssi PelkonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Mireia Gomez-BudiaA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Nelli-Noora VälimäkiA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Tuomas RauramaaInstitute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Pathology, Kuopio University Hospital, Kuopio, Finland.
Martine TherrienBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anne M KoivistoProgram in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland; Department of Neurosciences, University of Helsinki, Helsinki, Finland; Department of Geriatrics, Helsinki University Hospital, Helsinki, Finland.
Matthew TegtmeyerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sanna-Kaisa HerukkaInstitute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
Abdulraouf AbdulraoufBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Samuel E MarshF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Ralda NehmeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tarja MalmA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Beth StevensBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute (HHMI), Boston, MA 02115, USA.
Ville LeinonenInstitute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Evan Z MacoskoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Massachusetts General Hospital, Department of Psychiatry, Boston, MA 02114, USA. Electronic address: emacosko@broadinstitute.org.
Broad Institute · USUniversity of Eastern Finland · FIKuopio University Hospital · FIHarvard University · USBoston Children's Hospital · USHelsinki University Hospital · FIHoward Hughes Medical Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Characterizing the landscape of cell-type specific changes associated with Alzheimer's disease before death with single-cell genomicsF30AG069446 · NIA · HARVARD MEDICAL SCHOOL · PI KAMATH, TUSHAR VINOD · 2020 to 2023
$173k
NIA NIH HHS F30 AG069446NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Cellular perturbations underlying Alzheimer's disease (AD) are primarily studied in human postmortem samples and model organisms. Here, we generated a single-nucleus atlas from a rare cohort of cortical biopsies from living individuals with varying degrees of AD pathology. We next performed a systematic cross-disease and cross-species integrative analysis to identify a set of cell states that are specific to early AD pathology. These changes-which we refer to as the early cortical amyloid response-were prominent in neurons, wherein we identified a transitional hyperactive state preceding the loss of excitatory neurons, which we confirmed by acute slice physiology on independent biopsy specimens. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathology increased. Finally, both oligodendrocytes and pyramidal neurons upregulated genes associated with β-amyloid production and processing during this early hyperactive phase. Our integrative analysis provides an organizing framework for targeting circuit dysfunction, neuroinflammation, and amyloid production early in AD pathogenesis.

Indexed as

Alzheimer DiseaseFrontal LobeMicrogliaNeuronsAmyloidAmyloid beta-PeptidesBiopsyCell NucleusHumansPyramidal CellsSingle-Cell Gene Expression AnalysisAmyloidAmyloid beta-PeptidesAlzheimer’s diseaseamyloid pathologydisease systems biologyhuman cortexmeta-analysismicroglia disease responseneuronal hyperactivitysingle-nucleus RNA sequencingβ-amyloid metabolism

Identifiers

PMID37774681
PMCPMC11107481
OpenAlexW4387142556

What OpenQuestion holds

Textmetadata
LicenceTDM
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.