| Title: |
Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational study |
| Authors: |
Morenas-Rodríguez, E; Li, Y; Nuscher, B; Franzmeier, N; Xiong, C; Suárez-Calvet, M; Fagan, AM; Schultz, S; Gordon, BA; Benzinger, TLS; Hassenstab, J; McDade, E; Feederle, R; Karch, CM; Schlepckow, K; Morris, JC; Kleinberger, G; Nellgard, B; Vöglein, J; Blennow, K; Zetterberg, H; Ewers, M; Jucker, M; Levin, J; Bateman, RJ; Haass, C; Adams, S; Allegri, R; Araki, A; Barthelemy, N; Bechara, J; Berman, S; Bodge, C; Brandon, S; Brooks, W; Brosch, J; Buck, J; Buckles, V; Carter, K; Cash, L; Chen, C; Chhatwal, J; Chrem, P; Chua, J; Chui, H; Cruchaga, C; Day, GS; De La Cruz, C; Denner, D; Diffenbacher, A; Dincer, A; Donahue, T; Douglas, J; Duong, D; Egido, N; Esposito, B; Farlow, M; Feldman, B; Fitzpatrick, C; Flores, S; Fox, N; Franklin, E; Friedrichsen, N; Fujii, H; Gardener, S; Ghetti, B; Goate, A; Goldberg, S; Goldman, J; Gonzalez, A; Gräber-Sultan, S; Graff-Radford, N; Graham, M; Gray, J; Gremminger, E; Grilo, M; Groves, A; Häsler, L; Hellm, C; Herries, E; Hoechst-Swisher, L; Hofmann, A; Holtzman, D; Hornbeck, R; Igor, Y; Ihara, R; Ikeuchi, T; Ikonomovic, S; Ishii, K; Jack, C; Jerome, G; Johnson, E; Käser, S; Kasuga, K; Keefe, S; Klunk, W; Koeppe, R; Koudelis, D; Kuder-Buletta, E; Laske, C |
| Source: |
The Lancet Neurology , 21 (4) pp. 329-341. (2022) |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Dominantly Inherited Alzheimer Network |
| Description: |
BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease. METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer's disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models. FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10145962/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10145962/1/Zetterberg_Soluble%20TREM2%20in%20CSF%20and%20its%20association%20with%20other%20biomarkers%20and%20cognition%20in%20autosomal-dominant%20Alzheimer%27s%20disease_VoR.pdf; https://discovery.ucl.ac.uk/id/eprint/10145962/ |
| Rights: |
open |
| Accession Number: |
edsbas.E05ACFD9 |
| Database: |
BASE |