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@ARTICLE{Soltaninejad:283025,
      author       = {Soltaninejad, Mahdie and Dadar, Mahsa and Collins, D Louis
                      and Rajabli, Reza and Venkatraghavan, Vikram and Bouzigues,
                      Arabella and Russell, Lucy L and Foster, Phoebe H and
                      Ferry-Bolder, Eve and van Swieten, John C and Jiskoot, Lize
                      C and Seelaar, Harro and Sanchez-Valle, Raquel and Laforce,
                      Robert and Graff, Caroline and Galimberti, Daniela and
                      Vandenberghe, Rik and de Mendonça, Alexandre and
                      Tiraboschi, Pietro and Santana, Isabel and Gerhard,
                      Alexander and Levin, Johannes and Nacmias, Benedetta and
                      Otto, Markus and Bertoux, Maxime and Lebouvier, Thibaud and
                      Butler, Chris R and Ber, Isabelle Le and Finger, Elizabeth
                      and Tartaglia, Maria Carmela and Masellis, Mario and Rowe,
                      James B and Synofzik, Matthis and Moreno, Fermin and
                      Borroni, Barbara and Rohrer, Jonathan D and Iturria-Medina,
                      Yasser and Ducharme, Simon},
      collaboration = {Consortium, GENFI},
      title        = {{W}hite matter hyperintensities precede other biomarkers in
                      {GRN} frontotemporal dementia.},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {10},
      issn         = {1552-5260},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DZNE-2025-01437},
      pages        = {e70695},
      year         = {2025},
      abstract     = {Increased white matter hyperintensities (WMHs) have been
                      reported in genetic frontotemporal dementia (FTD) in small
                      studies, but the sequence of WMH abnormalities relative to
                      other biomarkers is unclear.Using a large dataset (n = 763
                      GENFI2 participants), we measured WMHs and examined them
                      across genetic FTD variants and stages. Cortical and
                      subcortical volumes were parcellated, and serum
                      neurofilament light chain (NfL) levels were measured.
                      Biomarker progression was assessed with discriminative
                      event-based and regression modeling.Symptomatic GRN carriers
                      showed elevated WMHs, primarily in the frontal lobe, while
                      no significant increase was observed in symptomatic C9orf72
                      or MAPT carriers. WMH abnormalities preceded NfL elevation,
                      ventricular enlargement, and cortical atrophy.
                      Longitudinally, baseline WMHs predicted subcortical changes,
                      while subcortical volumes did not predict WMH changes,
                      suggesting WMHs may precede neurodegeneration.WMHs are
                      elevated in a subset of GRN-associated FTD. When present,
                      they appear early and should be considered in disease
                      progression models.Elevated WMH volumes are found
                      predominantly in symptomatic GRN. WMH accumulation is mostly
                      observed in the frontal lobe. WMH abnormalities appear early
                      in GRN-associated FTD, before NfL, atrophy, and
                      ventriculomegaly. Longitudinally, WMH volumes can predict
                      subcortical changes, but not vice versa. WMHs are key early
                      markers in GRN-associated FTD and should be included in
                      progression models.},
      keywords     = {Humans / Frontotemporal Dementia: genetics / Frontotemporal
                      Dementia: pathology / Frontotemporal Dementia: diagnostic
                      imaging / White Matter: pathology / White Matter: diagnostic
                      imaging / Male / Female / Biomarkers: blood / Progranulins:
                      genetics / Middle Aged / Magnetic Resonance Imaging /
                      C9orf72 Protein: genetics / Neurofilament Proteins: blood /
                      Aged / Disease Progression / tau Proteins: genetics /
                      Atrophy / C9orf72 (Other) / FTD (Other) / GRN (Other) / MAPT
                      (Other) / biomarker sequence (Other) / dementia (Other) /
                      disease progression (Other) / early marker (Other) /
                      event‐based modeling (Other) / magnetic resonance imaging
                      (Other) / neurodegeneration (Other) / neurofilament light
                      chain (Other) / neuroimaging (Other) / progranulin (Other) /
                      white matter (Other) / Biomarkers (NLM Chemicals) /
                      Progranulins (NLM Chemicals) / GRN protein, human (NLM
                      Chemicals) / C9orf72 Protein (NLM Chemicals) / Neurofilament
                      Proteins (NLM Chemicals) / neurofilament protein L (NLM
                      Chemicals) / tau Proteins (NLM Chemicals) / C9orf72 protein,
                      human (NLM Chemicals) / MAPT protein, human (NLM Chemicals)},
      cin          = {Clinical Research (Munich) / AG Levin},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1111016},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41057914},
      pmc          = {pmc:PMC12504049},
      doi          = {10.1002/alz.70695},
      url          = {https://pub.dzne.de/record/283025},
}