Evidence map›Paper›PMID 41612483›Full record

ArticleAlzheimer's research & therapy2026

Glymphatic dysfunction links vascular pathology to Alzheimer's biomarkers and cognitive decline.

Sung Hoon Kang, Seongmi Kim, Young Ju Kim, Heejin Yoo, Eun Hye Lee, Hyemin Jang, Daeun Shin, Jihwan Yun, Jun Pyo Kim, Hee Jin Kim and 13 more

Abstract read
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. 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. Article
  2. 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

23 authors.

Sung Hoon Kang *Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Seongmi Kim *Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Young Ju KimDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Heejin YooDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Eun Hye LeeDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Hyemin JangDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Daeun ShinDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Jihwan YunDepartment of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
Jun Pyo KimDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Hee Jin KimDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Duk L NaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Henrick ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3, Göteborg, 413 90, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3, Göteborg, 413 90, Sweden.
Fernando Gonzalez-OrtizDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3, Göteborg, 413 90, Sweden.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3, Göteborg, 413 90, Sweden.
Theresa A DayEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Marco DueringMedical Image Analysis Center (MIAC), Department of Biomedical Engineering, University of Basel, Peterspl. 1, Basel, 4001, Switzerland.
Seong-Beom KohDepartment of Neurology, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-ro, Guro-gu, Seoul, 08308, Republic of Korea.
Sang-Young KimMR Clinical Science, Health Systems, Philips Healthcare, 30 Sowol-ro 2- gil, Yongsan District, Seoul, Republic of Korea.
Eung Yeop KimDepartment of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Sung Tae KimDepartment of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Beomseok SohnDepartment of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. beomseoksohn@gmail.com.
Sang Won SeoDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. sw72.seo@samsung.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVascular damage, including cerebral amyloid angiopathy (CAA) and non-amyloid cerebral small vessel disease (CSVD), has been linked to glymphatic dysfunction, which may contribute to Alzheimer's disease (AD) pathology and cognitive decline. We investigated the associations among vascular damage, glymphatic function measured by the DTI-ALPS (Diffusion Tensor Imaging-Analysis Along the Perivascular Space) index, AD plasma biomarkers, and cognitive decline.

methodsThis study includes 1,249 participants recruited from Samsung Medical Center. We performed linear regression analysis to identify factors associated with the DTI-ALPS index. Further, linear regression analysis with vascular imaging markers, including CAA and CSVD summary scores, as predictors and DTI-ALPS index as an outcome was performed to investigate the effect of vascular pathology on glymphatic function. We conducted mediation analyses to investigate whether the DTI-ALPS index mediates the effect of vascular imaging markers on plasma biomarkers (phosphorylated tau 217 [p-tau 217], glial fibrillary acidic protein [GFAP], and neurofilament light chain [NFL]). Additionally, mediation analyses with the DTI-ALPS index as a predictor, each plasma biomarker as a mediator, and annual MMSE or CDR-SOB change as an outcome to investigate whether plasma biomarkers mediate the effect of the DTI-ALPS index on longitudinal cognitive decline.

resultsFirst, the DTI-ALPS index was negatively associated with both CAA (β [95% CI] = -0.163 [-0.214, -0.112], p < 0.0001) and CSVD (β [95% CI] = -0.195 [-0.247, -0.143], p < 0.0001) summary scores after controlling for age, sex, BMI status, and APOE genotype. Second, the DTI-ALPS index fully mediated the relationship between these vascular markers and p-tau 217 (CSVD summary score, indirect effect β [95% CI] = 0.016 [0.010, 0.023], p < 0.001; CAA summary score, indirect effect β [95% CI] = 0.013 [0.008, 0.020], p < 0.001) and GFAP (CSVD summary score, indirect effect β [95% CI] = 0.015 [0.008, 0.022], p < 0.001; CAA summary score, indirect effect β [95% CI] = 0.012 [0.007, 0.019], p < 0.001), while partially mediating the relationship for NFL, regardless of Aβ uptake on PET. Finally, the DTI-ALPS index was significantly associated with cognitive decline and this association was partially mediated by plasma biomarkers.

conclusionsThese findings highlight glymphatic dysfunction as a key mechanism linking vascular pathology with tau, inflammation and neurodegeneration, independent of Aβ uptakes.

Indexed as

Alzheimer DiseaseCerebral Small Vessel DiseasesCognitive DysfunctionGlymphatic SystemAgedAged, 80 and overBiomarkersCerebral Amyloid AngiopathyDiffusion Tensor ImagingFemaleGlial Fibrillary Acidic ProteinHumansMaleNeurofilament Proteinstau ProteinsBiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinNeurofilament Proteinstau ProteinsAlzheimer’s diseaseDiffusion tensor imagingGlymphatic dysfunctionPlasma biomarkersVascular diseases

Identifiers

PMID41612483
PMCPMC13032277

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.