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@ARTICLE{Kobeleva:280782,
      author       = {Kobeleva, Xenia and Rowe, Bryan and Choupan, Jeiran and
                      Ringman, John M and Barisano, Giuseppe and Leone, Riccardo},
      title        = {{A}lterations in {MRI}-visible perivascular spaces precede
                      dementia diagnosis by 18 years in autosomal dominant
                      {A}lzheimer's disease.},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {8},
      issn         = {1552-5260},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DZNE-2025-00966},
      pages        = {e70588},
      year         = {2025},
      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.},
      keywords     = {Humans / Male / Female / Magnetic Resonance Imaging /
                      Alzheimer Disease: genetics / Alzheimer Disease: pathology /
                      Alzheimer Disease: diagnostic imaging / Cross-Sectional
                      Studies / Middle Aged / White Matter: diagnostic imaging /
                      White Matter: pathology / Glymphatic System: diagnostic
                      imaging / Glymphatic System: pathology / Basal Ganglia:
                      pathology / Basal Ganglia: diagnostic imaging / Mutation:
                      genetics / Aged / Amyloid beta-Peptides: cerebrospinal fluid
                      / tau Proteins: cerebrospinal fluid / Disease Progression /
                      Alzheimer's disease (Other) / autosomal dominant Alzheimer's
                      disease (Other) / cerebral small vessel disease (Other) /
                      dominantly inherited Alzheimer's disease (Other) / magnetic
                      resonance imaging (Other) / perivascular spaces (Other) /
                      Amyloid beta-Peptides (NLM Chemicals) / tau Proteins (NLM
                      Chemicals)},
      cin          = {AG Spottke / Clinical Research Platform (CRP) / Clinical
                      Research (Bonn)},
      ddc          = {610},
      cid          = {I:(DE-2719)1011103 / I:(DE-2719)1011401 /
                      I:(DE-2719)1011001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40851076},
      pmc          = {pmc:PMC12375433},
      doi          = {10.1002/alz.70588},
      url          = {https://pub.dzne.de/record/280782},
}