Evidence map›Paper›PMID 40671047›Full record

ArticleActa neuropathologica communications2025

Relationship between cerebral small vessel disease and proteinopathies in the medial temporal lobe.

Valentina Perosa, Jan Oltmer, Francesco Bax, Maarten L van den Berg, Corinne A Auger, Johanna Rotta, Romain Perbet, Jean Augustinack, Matthew P Frosch, Theresa Connors and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
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

13 authors.

Valentina PerosaJ. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA. VPEROSA@mgh.harvard.edu.ORCID 0000-0002-3551-5237
Jan OltmerBetterDoc GmbH, Kaiser-Wilhelm-Ring 30-32, 50367, Cologne, Germany.
Francesco BaxJ. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.
Maarten L van den BergMassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street 02129, Charlestown Navy Yard, Boston, MA, USA.
Corinne A AugerMassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street 02129, Charlestown Navy Yard, Boston, MA, USA.
Johanna RottaJ. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.
Romain PerbetMassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street 02129, Charlestown Navy Yard, Boston, MA, USA.
Jean AugustinackAthinoula A. Martinos Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street 02129, Charlestown, MA, USA.
Matthew P FroschNeuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street 02114, Boston, MA, USA.
Theresa ConnorsMassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street 02129, Charlestown Navy Yard, Boston, MA, USA.
Steven M GreenbergJ. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.
Bradley T HymanMassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street 02129, Charlestown Navy Yard, Boston, MA, USA.
Susanne J van VeluwJ. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Teresa Gomez-Isla · 2019 to 2026
$36.5M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathyR00AG059893 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI VAN VELUW, SUSANNE JANNEKE · 2020 to 2022
$745k
Understanding the mechanistic link between vascular dysfunction and Alzheimers disease-related protein accumulation in the medial temporal lobeK99AG080134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI PEROSA, VALENTINA · 2023 to 2024
$247k
Alzheimer's Association 243291NIA NIH HHS P30 AG062421NIGMS NIH HHS T32 GM144273NIH HHS K99AG080134NIH HHS R00AG059893
6 · The paper itself

Abstract

The medial temporal lobe (MTL) is strategically important for cognition and the pathogenesis of Alzheimer's Disease (AD). Cerebral small vessel disease (CSVD) independently contributes to cognitive impairment and is believed to play a role in AD. CSVD and proteinopathies related to AD often coexist in the MTL but neither the severity of CSVD, nor the associations between these pathologies have been quantitatively addressed in this brain region. We hypothesized that the severity of CSVD in the MTL is associated with the local burden of proteinopathies implicated in neurodegeneration (tau-tangles, amyloid-β-plaques, phospho-Tar-DNA-Binding-Protein-43 [pTDP-43]), regardless of disease stage. One potential mechanism linking CSVD and proteinopathies is a failure in perivascular brain clearance. Therefore, the relationship between CSVD and the enlargement of perivascular spaces (PVS) was investigated. AI-models and manual ratings were applied to digitized histological MTL-sections of 152 autopsy cases with and without Alzheimer's Disease Neuropathological Changes to quantify proteinopathies and the two common forms of CSVD, cerebral amyloid angiopathy (CAA) and arteriolosclerosis. The associations between CSVD and proteinopathies were assessed using linear-mixed-effects models. The relationship between CSVD and PVS enlargement was also investigated. Regional CAA-burden increased along Braak-stages and was positively associated with amyloid-β-plaques percentage area and tau-tangles density, irrespective of Braak-stage, but not with density of pTDP-43 inclusions. Local arteriolosclerosis severity was not associated with Braak-stages and had no direct effect on parenchymal proteinopathies. However, arteriolosclerosis severity and its interaction with CAA were positively associated with PVS enlargement. These results suggest that CAA, but not arteriolosclerosis, is more directly implicated in the pathophysiology of proteinopathies in the MTL. Moreover, arteriolosclerosis may contribute to perivascular clearance dysfunction.

Indexed as

Alzheimer DiseaseCerebral Small Vessel DiseasesTemporal LobeAgedAged, 80 and overAmyloid beta-PeptidesFemaleGlymphatic SystemHumansMaleMiddle AgedNeurofibrillary TanglesPlaque, Amyloidtau ProteinsAmyloid beta-Peptidestau ProteinsAlzheimer’s disease (AD)ArteriolosclerosisCerebral amyloid angiopathy (CAA)HippocampusMedial Temporal lobe (MTL)Perivascular space (PVS)

Identifiers

PMID40671047
PMCPMC12265290

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.