Evidence map›Paper›PMID 39069622›Full record

ArticleAlzheimer's research & therapy2024

The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy.

Anna Bonaterra-Pastra, Montse Solé, Silvia Lope-Piedrafita, Maria Lucas-Parra, Laura Castellote, Paula Marazuela, Olalla Pancorbo, David Rodríguez-Luna, Mar Hernández-Guillamon

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
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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

9 authors.

Anna Bonaterra-PastraNeurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Mediterranean Building, 1st floor, lab 106, Barcelona, 08035, Spain.
Montse SoléNeurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Mediterranean Building, 1st floor, lab 106, Barcelona, 08035, Spain.
Silvia Lope-PiedrafitaNuclear Magnetic Resonance Service, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Maria Lucas-ParraNeurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Mediterranean Building, 1st floor, lab 106, Barcelona, 08035, Spain.
Laura CastelloteDepartment of Clinical Biochemistry, Clinical Laboratories, Vall d'Hebron University Hospital, Barcelona, Spain.
Paula MarazuelaNeurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Mediterranean Building, 1st floor, lab 106, Barcelona, 08035, Spain.
Olalla PancorboStroke Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
David Rodríguez-LunaStroke Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
Mar Hernández-GuillamonNeurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Mediterranean Building, 1st floor, lab 106, Barcelona, 08035, Spain. Mar.hernandez.guillamon@vhir.org.

Funding

Agència de Gestió d'Ajuts Universitaris i de Recerca SGR2021/0656Instituto de Salud Carlos III (ISCIII) PI17/00275RICORS-ICTUS-Enfermedades Vasculares Cerebrales network funded by ISCIII RD21/0006/0007
6 · The paper itself

Abstract

backgroundCerebral amyloid angiopathy (CAA) is characterized by amyloid-β (Aβ) deposition in cerebral vessels, leading to lobar cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). Apolipoprotein J (ApoJ) is a multifunctional chaperone related to Aβ aggregation and clearance. Our study investigated the vascular impact of chronic recombinant human Apolipoprotein J (rhApoJ) treatment in a transgenic mouse model of β-amyloidosis with prominent CAA.

methodsTwenty-month-old APP23 C57BL/6 mice received 25 doses of rhApoJ (1 mg/kg) (n = 9) or saline (n = 8) intraperitoneally for 13 weeks, while Wild-type (WT) mice received saline (n = 13). Postmortem brains underwent T2*-weighted magnetic resonance imaging (MRI) to detect hemorrhagic lesions. Aβ levels and distribution, cerebral fibrinogen leakage, brain smooth muscle actin (sma), and plasma matrix metalloproteinases and inflammatory markers were analyzed after treatments. Additionally, plasma samples from 22 patients with lobar ICH were examined to determine the clinical relevance of the preclinical findings.

resultsrhApoJ-treated APP23 presented fewer cortical CMBs (50-300 μm diameter) (p = 0.012) and cortical larger hemorrhages (> 300 μm) (p = 0.002) than saline-treated mice, independently of Aβ brain levels. MRI-detected hemorrhagic lesions correlated with fibrinogen cerebral extravasation (p = 0.011). Additionally, rhApoJ-treated mice presented higher number of sma-positive vessels than saline-treated mice (p = 0.038). In rhApoJ-treated mice, human ApoJ was detected in plasma and in occasional leptomeningeal vessels, but not in the parenchyma, suggesting that its mechanism of action operates through the periphery. The administration of rhApoJ induced an increase in plasma Groα (p = 0.035) and MIP-1α (p = 0.035) levels, while lower MMP-12 (p = 0.046) levels, compared to the saline-treated group. In acute lobar ICH patients, MMP-12 plasma levels correlated with larger hemorrhage volume (p = 0.040) and irregular ICH shape (p = 0.036).

conclusionsChronic rhApoJ treatment in aged APP23 mice ameliorated CAA-related neurovascular damage by reducing the occurrence of CMB. We propose that rhApoJ may prevent blood-brain barrier (BBB) leakage and CMB appearance partly through circulating MMP-12 modulation.

Indexed as

Cerebral Amyloid AngiopathyCerebral HemorrhageDisease Models, AnimalMice, Inbred C57BLMice, TransgenicAgedAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainClusterinFemaleHumansMagnetic Resonance ImagingMaleMiceAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCLU protein, humanClusterinRecombinant ProteinsAmyloid-βApolipoprotein JCerebral amyloid AngiopathyCerebral microbleedsMMP-12

Identifiers

PMID39069622
PMCPMC11285315

What Socratic holds

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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 Socratic graph.