Journal Article

DZNE-2025-00966

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Alterations in MRI-visible perivascular spaces precede dementia diagnosis by 18 years in autosomal dominant Alzheimer's disease.

Kobeleva, X.DZNE* ; Rowe, B. ; Choupan, J. ; Ringman, J. M. ; Barisano, G. ; Leone, R. (First author)DZNE*

2025
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.70588

Abstract: Perivascular space (PVS) alterations are traditionally linked to cardiovascular risk factors and aging, but may also play a direct role in Alzheimer's disease (AD). To reduce confounding from age-related comorbidities, we examined PVSs in autosomal dominant AD (ADAD).In this cross-sectional study of 96 non-demented individuals (62 mutation carriers), we quantified PVS count fraction and mean diameter in white matter and basal ganglia using automated magnetic resonance imaging analysis. Linear mixed models assessed group differences along the disease course, adjusting for cardiovascular risk factors.Compared to non-carriers, mutation carriers showed lower PVS count fraction in white matter and basal ganglia, and larger PVS diameter in basal ganglia and the temporal lobe. Changes were evident up to 18 years before expected dementia onset and followed trajectories similar to amyloid beta 42 and tau biomarkers.ADAD is associated with early PVS alterations, suggesting perivascular changes may be integral to primary AD pathology.Autosomal dominant Alzheimer's disease (ADAD) mutation carriers have reduced magnetic resonance imaging-visible perivascular space (PVS) count fraction in the white matter and basal ganglia. ADAD mutation carriers show enlarged PVS in the basal ganglia and temporal white matter. PVS alterations start 18 years before the estimated time of dementia diagnosis. The spatial localization of PVS changes overlaps with regions of amyloid beta (Aβ) accumulation. The temporal evolution of PVS alterations aligns with Aβ and tau changes in the cerebrospinal fluid.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Cross-Sectional Studies (MeSH) ; Middle Aged (MeSH) ; White Matter: diagnostic imaging (MeSH) ; White Matter: pathology (MeSH) ; Glymphatic System: diagnostic imaging (MeSH) ; Glymphatic System: pathology (MeSH) ; Basal Ganglia: pathology (MeSH) ; Basal Ganglia: diagnostic imaging (MeSH) ; Mutation: genetics (MeSH) ; Aged (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; Disease Progression (MeSH) ; Alzheimer's disease ; autosomal dominant Alzheimer's disease ; cerebral small vessel disease ; dominantly inherited Alzheimer's disease ; magnetic resonance imaging ; perivascular spaces ; Amyloid beta-Peptides ; tau Proteins

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Contributing Institute(s):

1. Clinical Research Platform (CRP) (AG Spottke)
2. Clinical Research Platform (CRP) (Clinical Research Platform (CRP))
3. Clinical Research Coordination (Clinical Research (Bonn))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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