Evidence map›Paper›PMID 42791531›Full record

ArticleAlzheimer's research & therapy2026

Herpes simplex virus and kallikrein-related peptidases - a functional connection in Alzheimer's disease.

Oliver Goldhardt, Cinthia Mella Robles, Matthias Eberl, Tobias Dreyer, Antoninus Soosaipillai, Eleftherios P Diamandis, Josef Priller, Dieter Hoffmann, Jochen M Wettengel, Hianara Aracelly Bustamante and 5 more

Abstract read
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In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Oliver Goldhardt *Department of Neurology, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich (TUM), Ismaninger Str. 22, Munich, 81675, Germany. oliver.goldhardt@tum.de.ORCID http://orcid.org/0000-0002-3841-3391
Cinthia Mella Robles *Department of Neurology, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich (TUM), Ismaninger Str. 22, Munich, 81675, Germany.ORCID http://orcid.org/0000-0003-0237-4164
Matthias EberlDepartment of Neurology, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich (TUM), Ismaninger Str. 22, Munich, 81675, Germany.ORCID http://orcid.org/0009-0002-4483-8190
Tobias DreyerDepartment of Obstetrics & Gynecology, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich (TUM), Ismaninger Str. 22, Munich, 81675, Germany.ORCID http://orcid.org/0000-0002-5366-7859
Antoninus SoosaipillaiLunenfeld-Tanenbaum Research Institute, Sinai Health System, 60 Murray Street, Toronto, ON, M5T 3L9, Canada.
Eleftherios P DiamandisLunenfeld-Tanenbaum Research Institute, Sinai Health System, 60 Murray Street, Toronto, ON, M5T 3L9, Canada.ORCID http://orcid.org/0000-0002-1589-820X
Josef PrillerLaboratory of Molecular Psychiatry and DZNE, Charitéplatz 1, Berlin, 10117, Germany.ORCID http://orcid.org/0000-0001-7596-0979
Dieter HoffmannInstitute of Virology, TUM School of Medicine and Health, Helmholtz Munich / Technical University of Munich (TUM), Trogerstr. 30, Munich, 81675, Germany.ORCID http://orcid.org/0000-0003-3566-3341
Jochen M WettengelInstitute of Virology, TUM School of Medicine and Health, Helmholtz Munich / Technical University of Munich (TUM), Trogerstr. 30, Munich, 81675, Germany.ORCID http://orcid.org/0000-0002-4101-9280
Hianara Aracelly BustamanteLaboratory of Molecular Virology, Institute of Clinical Microbiology, Faculty of Medicine, University Austral de Chile, Los Laureles S/N, Isla Teja, Valdivia, 5110566, Chile.ORCID http://orcid.org/0000-0001-6932-7763
Paula SalazarLaboratory of Molecular Virology, Institute of Clinical Microbiology, Faculty of Medicine, University Austral de Chile, Los Laureles S/N, Isla Teja, Valdivia, 5110566, Chile.ORCID http://orcid.org/0009-0004-9614-1541
Markus ThalerDepartment of Laboratory Medicine, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich (TUM), Ismaninger Str. 22, Munich, 81675, Germany.ORCID http://orcid.org/0000-0002-5010-0718
Carola OtthLaboratory of Molecular Virology, Institute of Clinical Microbiology, Faculty of Medicine, University Austral de Chile, Los Laureles S/N, Isla Teja, Valdivia, 5110566, Chile.
Ingrid Pamela Ehrenfeld Slater *Laboratory of Cellular Pathology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, University Austral de Chile, Los Laureles S/N, Isla Teja, Valdivia, 5110566, Chile. ingridehrenfeld@uach.cl.ORCID http://orcid.org/0000-0002-2519-7570
Timo Grimmer *Department of Neurology, TUM University Hospital, TUM School of Medicine and Health, Technical University of Munich (TUM), Ismaninger Str. 22, Munich, 81675, Germany.ORCID http://orcid.org/0000-0002-6829-6253

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe viral hypothesis of Alzheimer's disease (AD) proposes that neurotropic pathogens may interact with amyloid and tau pathology, but the evidence remains controversial. We investigated whether cerebrospinal fluid (CSF) kallikrein-related peptidase 6 (KLK6) is associated with AD biomarkers and with an intrathecal anti-HSV immune response in patients with AD, and whether HSV-1 infection alters KLK6 expression in cell culture models.

methodsCSF KLKs and AD biomarkers were analyzed in patients with AD. HSV-1 serostatus and anti-HSV-1/2 CSF-to-serum antibody index (HSV-AI) were used as markers of previous or ongoing intrathecal anti-HSV immune response. In vitro, HSV-1 infection and KLK6 knockdown were examined in human cell models.

resultsCSF-KLK6 correlated with tau and amyloid biomarkers. In HSV-1-seropositive patients, HSV-AI was associated with CSF-KLK6, although the effect size was modest and the association was strongly context-dependent on the Aβ42/40 ratio. In vitro, productive HSV-1 infection induced and stabilized KLK6 protein expression, and KLK6 knockdown reduced HSV-1 protein expression and infectious progeny in HaCaT cells.

conclusionsKLK6 is associated with AD biomarkers and with an intrathecal anti-HSV immune response in a subset of patients with AD. The in vitro data support a functional relationship between HSV-1 infection and KLK6, but the clinical findings are associative and do not demonstrate ongoing CNS HSV-1 replication or causality. These findings warrant independent validation. However, this research provides further evidence for a role of HSV-1 in the pathophysiology of AD.

Indexed as

Alzheimer DiseaseHerpes SimplexHerpesvirus 1, HumanKallikreinsAgedAged, 80 and overAmyloid beta-PeptidesAnimalsBiomarkersFemaleHumansMalePeptide FragmentsRNA, Small Interferingtau ProteinsAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)BiomarkersKallikreinsKLK6 protein, humanPeptide FragmentsRNA, Small Interferingtau ProteinsAlpha-herpesvirinaeAlzheimer’s diseaseHerpes simplex virus type 1HSV1Kallikrein-related peptidaseKLK6Phospho tauSoluble amyloidTotal tau

Identifiers

PMID42791531
PMCPMC13615609

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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.