TY  - JOUR
AU  - Schirge, Philine Marie
AU  - Perneczky, Robert
AU  - Taoka, Toshiaki
AU  - Ruiz-Rizzo, Adriana L
AU  - Ersoezlue, Ersin
AU  - Forbrig, Robert
AU  - Guersel, Selim
AU  - Kurz, Carolin
AU  - Brendel, Matthias
AU  - Hellmann-Regen, Julian
AU  - Priller, Josef
AU  - Schneider, Anja
AU  - Jessen, Frank
AU  - Düzel, Emrah
AU  - Buerger, Katharina
AU  - Teipel, Stefan
AU  - Laske, Christoph
AU  - Peters, Oliver
AU  - Spruth, Eike
AU  - Fliessbach, Klaus
AU  - Rostamzadeh, Ayda
AU  - Glanz, Wenzel
AU  - Janowitz, Daniel
AU  - Kilimann, Ingo
AU  - Sodenkamp, Sebastian
AU  - Ewers, Michael
AU  - Rauchmann, Boris-Stephan
TI  - Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function.
JO  - Alzheimer's research & therapy
VL  - 17
IS  - 1
SN  - 1758-9193
CY  - London
PB  - BioMed Central
M1  - DZNE-2025-00437
SP  - 62
PY  - 2025
AB  - Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in Aβ clearance. The diffusion tensor image analysis along the perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate the glymphatic system in vivo, showing glymphatic insufficiency in AD. This study aimed to investigate alterations in the function of the glymphatic system in individuals with AD versus healthy controls (HC), and to explore its association with Aβ, cerebrovascular disease (CVD), white matter hyperintensities (WMH), and cognitive function.DTI MRI data from three independent study cohorts (ActiGliA: AD n = 16, Controls n = 18; DELCODE: AD n = 54, Controls n = 67; ADNI: AD n = 43, Controls n = 49) were used to evaluate the perivascular space (PVS) integrity; a potential biomarker for glymphatic activity. The DTI-Along the Perivascular Space technique was used to measure water diffusion along PVS providing an index to assess the efficiency of the glymphatic system's waste clearance function. WMH load was quantified in FLAIR MRI using the lesion segmentation tool. We quantified WMHs volume within our defined region of interest (ROI) and excluded participants with any WMHs to avoid confounding the ALPS-Index. Associations with cerebrospinal fluid (CSF) AD hallmark biomarkers, cognitive performance (MMSE) and clinical severity (CDR) were assessed.AD patients had a significantly lower ALPS-Index vs. healthy controls (ActiGliA: AD: mean = 1.22, SD = 0.12; Controls: mean = 1.36, SD = 0.14, p = 0.004; DELCODE: AD: mean = 1.26, SD = 0.18; Controls: mean = 1.34, SD = 0.2, p = 0.035; ADNI: AD: mean = 1.08, SD = 0.24; Controls: mean = 1.19, SD = 0.13, p = 0.008). The ALPS-Index was associated with CSF Aβ concentration, WMH number and MMSE and CDR. WMH, found in the ROIs correlated negatively with the ALPS-Index.This study highlights the potential of the DTI-ALPS-Index as a biomarker for glymphatic dysfunction in AD. It underscores the importance of considering vascular factors and the glymphatic system in the pathogenesis and diagnosis of AD as WMHs in the ROI could cause disturbances and inaccurate indices.
KW  - Humans
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: pathology
KW  - Female
KW  - Male
KW  - White Matter: diagnostic imaging
KW  - White Matter: pathology
KW  - Aged
KW  - Disease Progression
KW  - Glymphatic System: diagnostic imaging
KW  - Glymphatic System: pathology
KW  - Diffusion Tensor Imaging: methods
KW  - Cognition: physiology
KW  - Aged, 80 and over
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Amyloid beta-Peptides: metabolism
KW  - Magnetic Resonance Imaging: methods
KW  - Brain: diagnostic imaging
KW  - Brain: pathology
KW  - Alzheimer's disease (Other)
KW  - Amyloid-beta (Other)
KW  - Cognitive decline (Other)
KW  - Dementia (Other)
KW  - Diffusion tensor imaging (Other)
KW  - Perivascular space (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40098158
DO  - DOI:10.1186/s13195-025-01707-9
UR  - https://pub.dzne.de/record/277548
ER  -