Evidence map›Paper›PMID 32146679›Full record

ArticleMolecular neurobiology2020

Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer's Disease-Like Neuropathology in Tg2576 Mice.

Siok Lam Lim, Diana Nguyen Tran, Zanett Kieu, Christine Chen, Emmanuel Villanueva, Sagar Ghiaar, Victoria Gallup, Joannee Zumkehr, David H Cribbs, Carlos J Rodriguez-Ortiz and 1 more

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

Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

6 citing papers in PubMed, 8 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

11 authors at 2 institutions in 1 country.

Siok Lam LimDepartment of Medicine, Center for Occupational and Environmental Health, University of California, Irvine, CA, 92617, USA.
Diana Nguyen TranMolecular and Cell Biology, University of California, Merced, CA, 95343, USA.
Zanett KieuMolecular and Cell Biology, University of California, Merced, CA, 95343, USA.
Christine ChenMolecular and Cell Biology, University of California, Merced, CA, 95343, USA.
Emmanuel VillanuevaMolecular and Cell Biology, University of California, Merced, CA, 95343, USA.
Sagar GhiaarMolecular and Cell Biology, University of California, Merced, CA, 95343, USA.
Victoria GallupMolecular and Cell Biology, University of California, Merced, CA, 95343, USA.
Joannee ZumkehrDepartment of Medicine, Center for Occupational and Environmental Health, University of California, Irvine, CA, 92617, USA.
David H CribbsDepartment of Neurology, University of California, Irvine, CA, 92697, USA.
Carlos J Rodriguez-OrtizDepartment of Medicine, Center for Occupational and Environmental Health, University of California, Irvine, CA, 92617, USA.
Masashi KitazawaDepartment of Medicine, Center for Occupational and Environmental Health, University of California, Irvine, CA, 92617, USA. kitazawa@uci.edu.ORCID https://orcid.org/0000-0003-2165-8197
University of California, Merced · USUniversity of California, Irvine · US

Funding

Environmental copper exposure and its impact on microglial Abeta clearanceR01ES024331 · NIEHS · UNIVERSITY OF CALIFORNIA, MERCED · PI KITAZAWA, MASASHI · 2014 to 2018
$2.7M
Alzheimer's Association AARF-16-440554Alzheimer's Association NIRG-12-242598NIEHS NIH HHS R01 ES024331
6 · The paper itself

Abstract

Microglial dysregulation, pertaining to impairment in phagocytosis, clearance and containment of amyloid-β (Aβ), and activation of neuroinflammation, has been posited to contribute to the pathogenesis of Alzheimer's disease (AD). Detailed cellular mechanisms that are disrupted during the disease course to display such impairment in microglia, however, remain largely undetermined. We hypothesize that loss of hematopoietic cell kinase (HCK), a phagocytosis-regulating member of the Src family tyrosine kinases that mediate signals from triggering receptor expressed on myeloid cells 2 and other immunoreceptors, impairs microglial homeostasis and Aβ clearance, leading to the accelerated buildup of Aβ pathology and cognitive decline during the early stage of neuropathological development. To elucidate the pivotal role of HCK in AD, we generated a constitutive knockout of HCK in the Tg2576 mouse model of AD. We found that HCK deficiency accelerated cognitive decline along with elevated Aβ level and plaque burden, attenuated microglial Aβ phagocytosis, induced iNOS expression in microglial clusters, and reduced pre-synaptic protein at the hippocampal regions. Our findings substantiate that HCK plays a prominent role in regulating microglial neuroprotective functions and attenuating early AD neuropathology.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsDisease Models, AnimalDisease ProgressionExploratory BehaviorFemaleHomeostasisMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicrogliaMorris Water Maze TestMyeloid CellsAmyloid beta-PeptidesHck protein, mouseProto-Oncogene Proteins c-hckAlzheimer’s diseaseAmyloid-βHematopoietic cell kinaseMicrogliaTg2576 mice

Identifiers

PMID32146679
PMCPMC7187907
OpenAlexW3009457630

What OpenQuestion holds

Textmetadata
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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.