Evidence map›Paper›PMID 37333365›Full record

ArticlebioRxiv : the preprint server for biology2023

Early Alzheimer's disease pathology in human cortex is associated with a transient phase of distinct cell states.

Vahid Gazestani, Tushar Kamath, Naeem M Nadaf, S J Burris, Brendan Rooney, Antti Junkkari, Charles Vanderburg, Tuomas Rauramaa, Martine Therrien, Matthew Tegtmeyer and 9 more

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

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 9 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 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.
Naeem M NadafBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
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, Unit of Pathology, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Charles VanderburgBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Tuomas RauramaaInstitute of Clinical Medicine, Unit of Pathology, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Martine TherrienBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Matthew TegtmeyerBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Sanna-Kaisa HerukkaInstitute of Clinical Medicine, Unit of Pathology, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Abdulraouf AbdulraoufBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Samuel MarshF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115 USA.
Tarja MalmA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Mikko HiltunenInstitute of Biomedicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Ralda NehmeBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Beth StevensBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Ville LeinonenInstitute of Clinical Medicine, Unit of Pathology, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Evan Z MacoskoBroad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
Broad Institute · USUniversity of Eastern Finland · FIBoston Children's Hospital · USHarvard University · 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
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 GM144273
6 · The paper itself

Abstract

Cellular perturbations underlying Alzheimer's disease 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 Alzheimer's disease 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 transient state of hyperactivity preceding loss of excitatory neurons, which correlated with the selective loss of layer 1 inhibitory neurons. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathological burden increased. Lastly, both oligodendrocytes and pyramidal neurons upregulated genes associated with amyloid beta 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.

Identifiers

PMID37333365
PMCPMC10274680
OpenAlexW4379515600

What OpenQuestion holds

Textmetadata
LicenceCC BY-ND
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.