Evidence map›Paper›PMID 30909239›Full record

ArticleJournal of Alzheimer's disease : JAD2019

Choroid Plexus Acts as Gatekeeper for TREM2, Abnormal Accumulation of ApoE, and Fibrillary Tau in Alzheimer's Disease and in Down Syndrome Dementia.

Ruma Raha-Chowdhury, James W Henderson, Animesh Alexander Raha, Romina Vuono, Anastasia Bickerton, Elizabeth Jones, Robert Fincham, Kieren Allinson, Anthony Holland, Shahid H Zaman

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

Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.

  1. Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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  9. Choroid Plexus Pathophysiology.Annual review of pathology · 2025
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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

10 authors at 3 institutions in 1 country.

Ruma Raha-ChowdhuryCambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Cambridge, UK.
James W HendersonJohn van Geest Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK.
Animesh Alexander RahaJohn van Geest Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK.
Romina VuonoJohn van Geest Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK.
Anastasia BickertonCambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Cambridge, UK.
Elizabeth JonesCambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Cambridge, UK.
Robert FinchamClinical Pathology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Kieren AllinsonClinical Pathology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Anthony HollandCambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Cambridge, UK.
Shahid H ZamanCambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Cambridge, UK.
University of Cambridge · GBAddenbrooke's Hospital · GBCambridgeshire and Peterborough NHS Foundation Trust · GB

Funding

Department of HealthMedical Research Council RNAG/254
6 · The paper itself

Abstract

backgroundGenetic factors that influence Alzheimer's disease (AD) risk include mutations in TREM2 and allelic variants of Apolipoprotein E, influencing AD pathology in the general population and in Down syndrome (DS). Evidence shows that dysfunction of the choroid plexus may compromise the blood-cerebrospinal fluid (CSF) barrier, altering secretary, transport and immune function that can affect AD pathology.

objectiveTo investigate the genotype and phenotype of DS individuals in relation to choroid plexus damage and blood-CSF barrier leakage to identify markers that could facilitate early diagnosis of AD in DS.

methodsTo assess allele frequency and haplotype associations ApoE, Tau, TREM2, and HLA-DR were analyzed by SNP analysis in DS participants (n = 47) and controls (n = 50). The corresponding plasma protein levels were measured by ELISA. Postmortem brains from DS, AD, and age-matched controls were analyzed by immunohistochemistry.

resultsHaplotype analysis showed that individuals with Tau H1/H1 and ApoEɛ4 genotypes were more prevalent among DS participants with an earlier diagnosis of dementia (17%) compared to H1/H2 haplotypes (6%). Plasma TREM2 levels decreased whereas phospho-tau levels increased with age in DS. In AD and DS brain, insoluble tau and ApoE were found to accumulate in the choroid plexus.

conclusionAccumulation of tau and ApoE in the choroid plexus may increase the oligomerization rate of Aβ42 and impair tau trafficking, leading to AD pathology. We have identified a high-risk haplotype: ApoEɛ4, Tau/H1, and TREM2/T, that manifests age-related changes potentially opening a window for treatment many years prior to the manifestation of the AD dementia.

Indexed as

AdultAgedAged, 80 and overAlzheimer DiseaseApolipoproteins EChoroid PlexusDementiaDown SyndromeFemaleHumansMaleMembrane GlycoproteinsMiddle AgedPhosphorylationReceptors, Immunologictau ProteinsApolipoproteins EMembrane GlycoproteinsReceptors, Immunologictau ProteinsTREM2 protein, humanAlzheimer’s diseaseblood-brain barrierblood-CSF barrierchoroid plexusDown syndromehigh-risk haplotypeneuroinflammationtau traffickingTREM2white matter tract

Identifiers

PMID30909239
PMCPMC6598012
OpenAlexW2944252674

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.