Evidence map›Paper›PMID 26005850›Full record

ArticleNature neuroscience2015

Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance.

Zhen Zhao, Abhay P Sagare, Qingyi Ma, Matthew R Halliday, Pan Kong, Kassandra Kisler, Ethan A Winkler, Anita Ramanathan, Takahisa Kanekiyo, Guojun Bu and 12 more

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

Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 266 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
266citing papers in PubMed, 3 pooled it
23.6field-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

266 citing papers in PubMed, 3 syntheses or guidelines pooled it, 398 citations in OpenAlex.

  1. Pooled it
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  17. Cells · 2026
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206 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 1 country.

Zhen ZhaoZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Abhay P SagareZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Qingyi MaZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Matthew R HallidayZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Pan KongZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Kassandra KislerZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Ethan A Winkler1] Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. [2] Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Anita RamanathanZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Takahisa KanekiyoDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Guojun BuDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Nelly Chuqui OwensZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Sanket V RegeZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Gabriel SiZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Ashim AhujaZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Donghui ZhuDepartment of Chemical, Biological and Bioengineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, USA.
Carol A MillerDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Julie A SchneiderAlzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Manami Maeda1] Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of the City of Hope, Duarte, California, USA. [2] Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Takahiro Maeda1] Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of the City of Hope, Duarte, California, USA. [2] Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tohru SugawaraEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, and Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, California, USA.
Justin K IchidaEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, and Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, California, USA.
Berislav V ZlokovicZilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
University of Southern California · USJacksonville College · USBroad Center · USNorth Carolina Agricultural and Technical State University · USRush University Medical Center · US

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRASKIE, MEREDITH NICOLE · 1985 to 2019
$41.0M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Viral Vectors CoreP01NS074969 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2012 to 2021
$13.0M
TRANSGENIC MOUSE COREP01AG030128 · NIA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI WEEBER, EDWIN JOHN · 2009 to 2013
$9.4M
Cerebrovascular beta-Amyloidosis: A-beta CNS Transport PathwaysR37AG023084 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 2004 to 2013
$4.6M
ApoE Receptor Pathways to Intraneuronal AbetaR01AG027924 · NIA · WASHINGTON UNIVERSITY · PI LI, YONGHE · 2006 to 2021
$3.7M
Alzheimer's Abeta, apolipoproteins and blood-brain barrierR37NS034467 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 2007 to 2013
$3.4M
BRAIN LIPID METABOLISM, DENDRITES AND SYNAPSES IN AGING AND ALZHEIMER'S DISEASER01AG035355 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN · 2010 to 2019
$3.1M
ApoE isoform-specific therapy for Alzheimer diseaseRF1AG046205 · NIA · MAYO CLINIC JACKSONVILLE · PI ZHAO, NA · 2019 to 2019
$3.1M
The role of pericytes in the adult and the aging brainR01AG039452 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 2011 to 2015
$1.6M
ApoE isoform-specific therapy for Alzheimer diseaseR01AG046205 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN · 2013 to 2017
$1.6M
Brain Pericyte and Amyloid-beta Peptide InteractionSC2NS082475 · NINDS · NORTH CAROLINA AGRI & TECH ST UNIV · PI ZHU, DONGHUI · 2012 to 2014
$421k
NIA NIH HHS P01 AG030128NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG027924NIA NIH HHS R01AG027924NIA NIH HHS R01 AG035355NIA NIH HHS R01AG035355NIA NIH HHS R01 AG039452NIA NIH HHS R01AG039452NIA NIH HHS R01 AG046205NIA NIH HHS R37 AG023084NIA NIH HHS R37AG23084NIA NIH HHS RF1 AG046205NINDS NIH HHS P01 NS074969NINDS NIH HHS R00NS07743NINDS NIH HHS R37 NS034467NINDS NIH HHS R37NS34467
6 · The paper itself

Abstract

PICALM is a highly validated genetic risk factor for Alzheimer's disease (AD). We found that reduced expression of PICALM in AD and murine brain endothelium correlated with amyloid-β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminished Aβ clearance across the murine blood-brain barrier (BBB) and accelerated Aβ pathology in a manner that was reversible by endothelial PICALM re-expression. Using human brain endothelial monolayers, we found that PICALM regulated PICALM/clathrin-dependent internalization of Aβ bound to the low density lipoprotein receptor related protein-1, a key Aβ clearance receptor, and guided Aβ trafficking to Rab5 and Rab11, leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD-derived endothelial monolayers, which was reversible by adenoviral-mediated PICALM transfer. Inducible pluripotent stem cell-derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance, which has implications for Aβ brain homeostasis and clearance therapy.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBlood-Brain BarrierCapillariesCerebral CortexEndothelium, VascularHomeostasisHumansMetabolic Clearance RateMiceMice, KnockoutMonomeric Clathrin Assembly ProteinsPluripotent Stem CellsTranscytosisAmyloid beta-PeptidesMonomeric Clathrin Assembly ProteinsPICALM protein, humanPICALM protein, mouse

Identifiers

PMID26005850
PMCPMC4482781
OpenAlexW1516940938

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.