Home > Publications Database > Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease. > print

001     278999
005     20250615001324.0
024 7 _ |a 10.1007/s00401-025-02890-7
|2 doi
024 7 _ |a pmid:40459787
|2 pmid
024 7 _ |a 0001-6322
|2 ISSN
024 7 _ |a 1432-0533
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024 7 _ |a altmetric:177790449
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037 _ _ |a DZNE-2025-00663
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Chen, Charles D
|b 0
245 _ _ |a Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease.
260 _ _ |a Heidelberg
|c 2025
|b Springer
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Alzheimer disease
|2 Other
650 _ 7 |a Anti-amyloid-β monoclonal antibodies
|2 Other
650 _ 7 |a CSF
|2 Other
650 _ 7 |a Clinical trial
|2 Other
650 _ 7 |a Digital pathology
|2 Other
650 _ 7 |a PiB PET
|2 Other
650 _ 7 |a Antibodies, Monoclonal, Humanized
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a gantenerumab
|0 4DF060P933
|2 NLM Chemicals
650 _ 7 |a solanezumab
|0 5D6PWO0333
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Antibodies, Monoclonal, Humanized: therapeutic use
|2 MeSH
650 _ 2 |a Alzheimer Disease: drug therapy
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: metabolism
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Brain: drug effects
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Immunohistochemistry
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
700 1 _ |a Franklin, Erin E
|b 1
700 1 _ |a Li, Yan
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700 1 _ |a Joseph-Mathurin, Nelly
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700 1 _ |a Burns, Aime L
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700 1 _ |a Hobbs, Diana A
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700 1 _ |a McCullough, Austin A
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700 1 _ |a Schultz, Stephanie A
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700 1 _ |a Xiong, Chengjie
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700 1 _ |a Wang, Guoqiao
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700 1 _ |a Masellis, Mario
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700 1 _ |a Hsiung, Ging-Yuek Robin
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700 1 _ |a Gauthier, Serge
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700 1 _ |a Berman, Sarah B
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700 1 _ |a Roberson, Erik D
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700 1 _ |a Honig, Lawrence S
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700 1 _ |a Clarnette, Roger
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700 1 _ |a Ringman, John M
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700 1 _ |a Galvin, James E
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700 1 _ |a Brooks, William
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700 1 _ |a Suzuki, Kazushi
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700 1 _ |a Black, Sandra
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700 1 _ |a Levin, Johannes
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700 1 _ |a Aggarwal, Neelum T
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700 1 _ |a Jucker, Mathias
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700 1 _ |a Frosch, Matthew P
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700 1 _ |a Kofler, Julia K
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700 1 _ |a White, Charles
|b 27
700 1 _ |a Keene, C Dirk
|b 28
700 1 _ |a Chen, Jie
|b 29
700 1 _ |a Daniels, Alisha
|b 30
700 1 _ |a Gordon, Brian A
|b 31
700 1 _ |a Ibanez, Laura
|b 32
700 1 _ |a Karch, Celeste M
|b 33
700 1 _ |a Llibre-Guerra, Jorge
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700 1 _ |a McDade, Eric
|b 35
700 1 _ |a Morris, John C
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700 1 _ |a Supnet-Bell, Charlene
|b 37
700 1 _ |a Allegri, Ricardo F
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700 1 _ |a Lee, Jae-Hong
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700 1 _ |a Day, Gregory S
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700 1 _ |a Lopera, Francisco
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700 1 _ |a Roh, Jee Hoon
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700 1 _ |a Schofield, Peter R
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700 1 _ |a Mills, Susan
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700 1 _ |a Benzinger, Tammie L S
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700 1 _ |a Bateman, Randall J
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700 1 _ |a Perrin, Richard J
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700 1 _ |a Team, DIAN-TU Study
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700 1 _ |a Bateman, Randall
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700 1 _ |a Daniels, Alisha J
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700 1 _ |a Courtney, Laura
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700 1 _ |a Llibre-Guerra, Jorge J
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700 1 _ |a Xiong, Chengie
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700 1 _ |a Xu, Xiong
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700 1 _ |a Lu, Ruijin
|b 56
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700 1 _ |a Gremminger, Emily
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700 1 _ |a Jerome, Gina
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700 1 _ |a Herries, Elizabeth
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700 1 _ |a Stauber, Jennifer
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700 1 _ |a Baker, Bryce
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700 1 _ |a Minton, Matthew
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700 1 _ |a Cruchaga, Carlos
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700 1 _ |a Goate, Alison M
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700 1 _ |a Renton, Alan E
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700 1 _ |a Picarello, Danielle M
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700 1 _ |a Benzinger, Tammie
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700 1 _ |a Hornbeck, Russell
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700 1 _ |a Hassenstab, Jason
|b 69
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700 1 _ |a Smith, Jennifer
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700 1 _ |a Stout, Sarah
|b 71
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700 1 _ |a Aschenbrenner, Andrew J
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700 1 _ |a Marsh, Jacob
|b 73
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700 1 _ |a Holtzman, David M
|b 74
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700 1 _ |a Barthelemy, Nicolas
|b 75
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700 1 _ |a Xu, Jinbin
|b 76
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700 1 _ |a Noble, James M
|b 77
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700 1 _ |a Ikonomovic, Snezana
|b 78
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700 1 _ |a Nadkarni, Neelesh K
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700 1 _ |a Graff-Radford, Neill R
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700 1 _ |a Farlow, Martin
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700 1 _ |a Chhatwal, Jasmeer P
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700 1 _ |a Ikeuchi, Takeshi
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700 1 _ |a Kasuga, Kensaku
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700 1 _ |a Niimi, Yoshiki
|b 85
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700 1 _ |a Huey, Edward D
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700 1 _ |a Salloway, Stephen
|b 87
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700 1 _ |a Brooks, William S
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700 1 _ |a Bechara, Jacob A
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700 1 _ |a Martins, Ralph
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700 1 _ |a Fox, Nick C
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700 1 _ |a Cash, David M
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700 1 _ |a Ryan, Natalie S
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700 1 _ |a Laske, Christoph
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700 1 _ |a Hofmann, Anna
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700 1 _ |a Kuder-Buletta, Elke
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700 1 _ |a Gräber-Sultan, Susanne
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700 1 _ |a Obermueller, Ulrike
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700 1 _ |a Roedenbeck, Yvonne
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700 1 _ |a Vӧglein, Jonathan
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700 1 _ |a Sanchez-Valle, Raquel
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700 1 _ |a Rosa-Neto, Pedro
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700 1 _ |a Mendez, Patricio Chrem
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700 1 _ |a Surace, Ezequiel
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700 1 _ |a Vazquez, Silvia
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700 1 _ |a Leon, Yudy Milena
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700 1 _ |a Ramirez, Laura
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700 1 _ |a Aguillon, David
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700 1 _ |a Levey, Allan I
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700 1 _ |a Johnson, Erik C B
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700 1 _ |a Seyfried, Nicholas T
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700 1 _ |a Ringman, John
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700 1 _ |a Fagan, Anne M
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700 1 _ |a Mori, Hiroshi
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773 _ _ |a 10.1007/s00401-025-02890-7
|g Vol. 149, no. 1, p. 57
|0 PERI:(DE-600)1458410-4
|n 1
|p 57
|t Acta neuropathologica
|v 149
|y 2025
|x 0001-6322
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