| Title: |
Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease The DIAN-TU-001 Randomized Clinical Trial |
| Authors: |
Wagemann, O; Liu, H; Wang, G; Shi, X; Bittner, T; Scelsi, MA; Farlow, MR; Clifford, DB; Supnet-Bell, C; Santacruz, AM; Aschenbrenner, AJ; Hassenstab, JJ; Benzinger, TLS; Gordon, BA; Coalier, KA; Cruchaga, C; Ibanez, L; Perrin, RJ; Xiong, C; Li, Y; Morris, JC; Lah, JJ; Berman, SB; Roberson, ED; van Dyck, CH; Galasko, D; Gauthier, S; Hsiung, GYR; Brooks, WS; Pariente, J; Mummery, CJ; Day, GS; Ringman, JM; Mendez, PC; St. George-Hyslop, P; Fox, NC; Suzuki, K; Okhravi, HR; Chhatwal, J; Levin, J; Jucker, M; Sims, JR; Holdridge, KC; Proctor, NK; Yaari, R; Andersen, SW; Mancini, M; Llibre-Guerra, J; Bateman, RJ; McDade, E |
| Source: |
JAMA Neurology (2024) (In press). |
| Publisher Information: |
American Medical Association (AMA) |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Dominantly Inherited Alzheimer Network–Trials Unit |
| Description: |
IMPORTANCE Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). OBJECTIVE To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. DESIGN, SETTING, AND PARTICIPANTS From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed. INTERVENTIONS In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks. MAIN OUTCOMES AND MEASURES Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3–like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL. RESULTS Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = −242.43 [48.04] pg/mL; P < .001); reduced plasma GFAP level at year 1 (mean [SD] β = −0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] β = −0.03 [0.01] ng/mL; P = .002), and ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10192051/1/jamaneurology_wagemann_2024_oi_240021_1713395544.70408.pdf; https://discovery.ucl.ac.uk/id/eprint/10192051/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10192051/1/jamaneurology_wagemann_2024_oi_240021_1713395544.70408.pdf; https://discovery.ucl.ac.uk/id/eprint/10192051/ |
| Rights: |
open |
| Accession Number: |
edsbas.38E80A27 |
| Database: |
BASE |