eprintid: 10089787 rev_number: 23 eprint_status: archive userid: 608 dir: disk0/10/08/97/87 datestamp: 2020-01-17 15:31:42 lastmod: 2021-09-17 22:01:32 status_changed: 2020-01-17 15:31:42 type: article metadata_visibility: show creators_name: Cavedo, E creators_name: Lista, S creators_name: Houot, M creators_name: Vergallo, A creators_name: Grothe, MJ creators_name: Teipel, S creators_name: Zetterberg, H creators_name: Blennow, K creators_name: Habert, M-O creators_name: Potier, MC creators_name: Dubois, B creators_name: Hampel, H creators_name: INSIGHT-preAD Study Group and the Alzheimer Precision Medicine I, title: Plasma tau correlates with basal forebrain atrophy rates in people at risk for Alzheimer disease ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Alzheimer's disease, Volumetric MRI note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: OBJECTIVE: To investigate whether baseline concentrations of plasma total tau (t-tau) and neurofilament light (NfL) chain proteins are associated with annual percent change (APC) of the basal forebrain cholinergic system (BFCS) in cognitively intact older adults at risk for Alzheimer disease (AD). METHODS: This was a large-scale study of 276 cognitively intact older adults from the monocentric INSIGHT-preAD (Investigation of Alzheimer's Predictors in Subjective Memory Complainers) cohort. Participants underwent baseline assessment of plasma t-tau and NfL concentrations as well as baseline and 24-month follow-up MRI scans. Linear models with and without influential observations (calculated using the Cook distance) were carried out to investigate the effect of plasma NfL and t-tau concentrations, and their interaction effect with β-amyloid status and APOE genotype, on the APC of the whole BFCS and its anterior (Ch1/2) and posterior (Ch4) subdivisions separately. RESULTS: Higher plasma t-tau concentrations at baseline were associated with higher BFCS rate of atrophy (model without influencers: n = 251, F value = 4.6815; p value = 0.031). Subregional analyses showed similar results for both the APC of the Ch1/2 (model without influencers: n = 256, F value = 3.9535, p corrected = 0.047) and Ch4 BFCS sectors (model without influencers: n = 253, F value = 4.9090, p corrected = 0.047). Baseline NfL, β-amyloid load, and APOE ε4 carrier status did not affect APC of the BFCS. CONCLUSION: Increased concentrations of baseline plasma t-tau may predict in vivo structural BFCS atrophy progression in older adults at risk for AD, independently of β-amyloid status and APOE genotype. date: 2020-01-07 date_type: published official_url: https://doi.org/10.1212/WNL.0000000000008696 full_text_type: other language: eng verified: verified_manual elements_id: 1729556 doi: 10.1212/WNL.0000000000008696 pii: WNL.0000000000008696 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Allington-Smith, Dominic actors_id: DAALL44 actors_role: owner full_text_status: restricted publication: Neurology volume: 94 number: 1 pagerange: e30-e41 event_location: United States citation: Cavedo, E; Lista, S; Houot, M; Vergallo, A; Grothe, MJ; Teipel, S; Zetterberg, H; ... INSIGHT-preAD Study Group and the Alzheimer Precision Medicine I; + view all <#> Cavedo, E; Lista, S; Houot, M; Vergallo, A; Grothe, MJ; Teipel, S; Zetterberg, H; Blennow, K; Habert, M-O; Potier, MC; Dubois, B; Hampel, H; INSIGHT-preAD Study Group and the Alzheimer Precision Medicine I; - view fewer <#> (2020) Plasma tau correlates with basal forebrain atrophy rates in people at risk for Alzheimer disease. Neurology , 94 (1) e30-e41. 10.1212/WNL.0000000000008696 <https://doi.org/10.1212/WNL.0000000000008696>. document_url: https://discovery.ucl.ac.uk/id/eprint/10089787/3/Zetterberg_Cavedo.pdf