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@ARTICLE{Chen:278999,
      author       = {Chen, Charles D and Franklin, Erin E and Li, Yan and
                      Joseph-Mathurin, Nelly and Burns, Aime L and Hobbs, Diana A
                      and McCullough, Austin A and Schultz, Stephanie A and Xiong,
                      Chengjie and Wang, Guoqiao and Masellis, Mario and Hsiung,
                      Ging-Yuek Robin and Gauthier, Serge and Berman, Sarah B and
                      Roberson, Erik D and Honig, Lawrence S and Clarnette, Roger
                      and Ringman, John M and Galvin, James E and Brooks, William
                      and Suzuki, Kazushi and Black, Sandra and Levin, Johannes
                      and Aggarwal, Neelum T and Jucker, Mathias and Frosch,
                      Matthew P and Kofler, Julia K and White, Charles and Keene,
                      C Dirk and Chen, Jie and Daniels, Alisha and Gordon, Brian A
                      and Ibanez, Laura and Karch, Celeste M and Llibre-Guerra,
                      Jorge and McDade, Eric and Morris, John C and Supnet-Bell,
                      Charlene and Allegri, Ricardo F and Lee, Jae-Hong and Day,
                      Gregory S and Lopera, Francisco and Roh, Jee Hoon and
                      Schofield, Peter R and Mills, Susan and Benzinger, Tammie L
                      S and Bateman, Randall J and Perrin, Richard J},
      collaboration = {Team, DIAN-TU Study and Team, DIAN-Obs Study},
      othercontributors = {Bateman, Randall and Daniels, Alisha J and Courtney, Laura
                          and Llibre-Guerra, Jorge J and Xiong, Chengie and Xu, Xiong
                          and Lu, Ruijin and Gremminger, Emily and Jerome, Gina and
                          Herries, Elizabeth and Stauber, Jennifer and Baker, Bryce
                          and Minton, Matthew and Cruchaga, Carlos and Goate, Alison M
                          and Renton, Alan E and Picarello, Danielle M and Benzinger,
                          Tammie and Hornbeck, Russell and Hassenstab, Jason and
                          Smith, Jennifer and Stout, Sarah and Aschenbrenner, Andrew J
                          and Marsh, Jacob and Holtzman, David M and Barthelemy,
                          Nicolas and Xu, Jinbin and Noble, James M and Ikonomovic,
                          Snezana and Nadkarni, Neelesh K and Graff-Radford, Neill R
                          and Farlow, Martin and Chhatwal, Jasmeer P and Ikeuchi,
                          Takeshi and Kasuga, Kensaku and Niimi, Yoshiki and Huey,
                          Edward D and Salloway, Stephen and Brooks, William S and
                          Bechara, Jacob A and Martins, Ralph and Fox, Nick C and
                          Cash, David M and Ryan, Natalie S and Laske, Christoph and
                          Hofmann, Anna and Kuder-Buletta, Elke and Gräber-Sultan,
                          Susanne and Obermueller, Ulrike and Roedenbeck, Yvonne and
                          Vӧglein, Jonathan and Sanchez-Valle, Raquel and Rosa-Neto,
                          Pedro and Mendez, Patricio Chrem and Surace, Ezequiel and
                          Vazquez, Silvia and Leon, Yudy Milena and Ramirez, Laura and
                          Aguillon, David and Levey, Allan I and Johnson, Erik C B and
                          Seyfried, Nicholas T and Ringman, John and Fagan, Anne M and
                          Mori, Hiroshi},
      title        = {{I}mmunohistochemical evaluation of a trial of gantenerumab
                      or solanezumab in dominantly inherited {A}lzheimer disease.},
      journal      = {Acta neuropathologica},
      volume       = {149},
      number       = {1},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2025-00663},
      pages        = {57},
      year         = {2025},
      abstract     = {Clinical trials of anti-amyloid-β (Aβ) monoclonal
                      antibodies in Alzheimer disease (AD) infer target engagement
                      from Aβ positron emission tomography (PET) and/or fluid
                      biomarkers such as cerebrospinal fluid (CSF) Aβ42/40.
                      However, these biomarkers measure brain Aβ deposits
                      indirectly and/or incompletely. In contrast, neuropathologic
                      assessments allow direct investigation of treatment effects
                      on brain Aβ deposits-and on potentially myriad 'downstream'
                      pathologic features. From a clinical trial of anti-Aβ
                      monoclonal antibodies in dominantly inherited AD (DIAD), in
                      the largest study of its kind, we measured
                      immunohistochemistry area fractions (AFs) for Aβ deposits
                      (10D5), tauopathy (PHF1), microgliosis (IBA1), and
                      astrocytosis (GFAP) in 10 brain regions from 10 trial
                      cases-gantenerumab (n = 4), solanezumab (n = 4), placebo/no
                      treatment (n = 2)-and 10 DIAD observational study cases.
                      Strikingly, in proportion to total drug received, Aβ
                      deposit AFs were significantly lower in the gantenerumab arm
                      versus controls in almost all areas examined, including
                      frontal, temporal, parietal, and occipital cortices,
                      anterior cingulate, hippocampus, caudate, putamen, thalamus,
                      and cerebellar gray matter; only posterior cingulate and
                      cerebellar white matter comparisons were non-significant. In
                      contrast, AFs of tauopathy, microgliosis, and astrocytosis
                      showed no differences across groups. Our results demonstrate
                      with direct histologic evidence that gantenerumab treatment
                      in DIAD can reduce parenchymal Aβ deposits throughout the
                      brain in a dose-dependent manner, suggesting that more
                      complete removal may be possible with earlier and more
                      aggressive treatment regimens. Although AFs of tauopathy,
                      microgliosis, and astrocytosis showed no clear response to
                      partial Aβ removal in this limited autopsy cohort, future
                      examination of these cases with more sensitive techniques
                      (e.g., mass spectrometry) may reveal more subtle
                      'downstream' effects.},
      keywords     = {Humans / Antibodies, Monoclonal, Humanized: therapeutic use
                      / Alzheimer Disease: drug therapy / Alzheimer Disease:
                      pathology / Alzheimer Disease: genetics / Alzheimer Disease:
                      metabolism / Male / Female / Amyloid beta-Peptides:
                      metabolism / Aged / Brain: pathology / Brain: drug effects /
                      Brain: metabolism / Middle Aged / Immunohistochemistry /
                      Aged, 80 and over / Alzheimer disease (Other) /
                      Anti-amyloid-β monoclonal antibodies (Other) / CSF (Other)
                      / Clinical trial (Other) / Digital pathology (Other) / PiB
                      PET (Other) / Antibodies, Monoclonal, Humanized (NLM
                      Chemicals) / Amyloid beta-Peptides (NLM Chemicals) /
                      gantenerumab (NLM Chemicals) / solanezumab (NLM Chemicals)},
      cin          = {AG Levin / Clinical Research (Munich) / AG Jucker},
      ddc          = {610},
      cid          = {I:(DE-2719)1111016 / I:(DE-2719)1111015 /
                      I:(DE-2719)1210001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40459787},
      doi          = {10.1007/s00401-025-02890-7},
      url          = {https://pub.dzne.de/record/278999},
}