Evidence map›Paper›PMID 42214342›Full record

ArticleCell2026

Physiological brain clearance architecture revealed by neuronal protein tracing.

Yuichi Chayama, Nalini R Rao, Daniela Perla, Zimo Zhang, Madigan Reid, Sophia Nelson, Xinlan Wen, Bella Ding, Jessica Blumenfeld, Amanda Apolonio and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

20 authors.

Yuichi ChayamaGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Nalini R RaoGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Daniela PerlaGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Zimo ZhangGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Madigan ReidGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Sophia NelsonGladstone Institute of Neurological Disease, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Xinlan WenGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Bella DingGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Jessica BlumenfeldGladstone Institute of Neurological Disease, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Amanda ApolonioGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Sahith DoddipalliGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Haoyue ZhouGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Sena Gül TurhanInstitute for Intelligent Biotechnologies, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Pu-Yun ShihDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Matthias BrendelDepartment of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Ying-Hui FuDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
Ali ErtürkInstitute for Intelligent Biotechnologies, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; German Research Center for Environmental Health, Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; School of Medicine, Koç University, İstanbul, Turkey.
Zeynep Ilgin KolabasInstitute for Intelligent Biotechnologies, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany; Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Yadong HuangGladstone Institute of Neurological Disease, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Andrew C YangGladstone Institute of Neurological Disease, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Bakar Aging Research Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: andrew.yang@gladstone.ucsf.edu.

Funding

Vascular-immune mechanisms of cerebral amyloid angiopathy and Alzheimer's pathologyRF1NS139975 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI ARFANAKIS, KONSTANTINOS, BLURTON-JONES, MATHEW MARK · 2024 to 2024
$5.4M
Elucidating microvascular contributions to cognitive impairment at single-cell resolutionR01NS128909 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Andrew Chris Yang · 2022 to 2026
$4.5M
Molecular tools to decipher communication across the blood-brain barrierDP5OD033381 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YANG, ANDREW CHRIS · 2022 to 2025
$2.1M
NIH HHS DP5 OD033381NINDS NIH HHS R01 NS128909NINDS NIH HHS RF1 NS139975
6 · The paper itself

Abstract

The brain must efficiently clear protein waste to maintain homeostasis, yet physiological drainage pathways remain poorly defined. Standard tracer injection approaches may not reflect endogenous efflux. Here, we develop a non-invasive genetic system to trace neuron-derived protein clearance from the brain to cerebrospinal fluid (CSF) and border tissues. We identify distinct drainage routes and border hotspots missed by tracer injection, confirmed by bioorthogonal labeling of endogenous neuronal proteins. Pulse-chase kinetics reveal slow skull outflow versus rapid dural and nasal clearance. Transcriptomic analyses uncover border cells sampling neuronal antigens, including tolerogenic skull-resident B cells. Region-restricted reporter expression demonstrates compartmentalized clearance following a "nearest exit" principle, where anatomical origin dictates drainage pathway. Disease disrupts clearance through distinct mechanisms: inflammation drives vascular leakage into blood, while amyloid pathology causes parenchymal retention and border exit obstruction. These findings define brain clearance as a compartmentalized system of organized pathways and immune niches whose dysfunction may underlie regional vulnerability in neurological disease.

Indexed as

BrainNerve Tissue ProteinsNeuronsAnimalsHumansMiceMice, Inbred C57BLNerve Tissue ProteinsAlzheimer’s diseasebrain bordersbrain waste clearancecerebrospinal fluidCNS drainageduraimmune toleranceneuroimmunologyskull

Identifiers

PMID42214342
PMCPMC13225612

What Socratic 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 Socratic graph.