eprintid: 10194799 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/19/47/99 datestamp: 2024-07-19 10:11:01 lastmod: 2024-07-19 10:11:01 status_changed: 2024-07-19 10:11:01 type: article metadata_visibility: show sword_depositor: 699 creators_name: Duggan, Michael R creators_name: Gomez, Gabriela T creators_name: Joynes, Cassandra M creators_name: Bilgel, Murat creators_name: Chen, Jingsha creators_name: Fattorelli, Nicola creators_name: Hohman, Timothy J creators_name: Mancuso, Renzo creators_name: Cordon, Jenifer creators_name: Castellano, Tonnar creators_name: Koran, Mary Ellen I creators_name: Candia, Julián creators_name: Lewis, Alexandria creators_name: Moghekar, Abhay creators_name: Ashton, Nicholas J creators_name: Kac, Przemysław R creators_name: Karikari, Thomas K creators_name: Blennow, Kaj creators_name: Zetterberg, Henrik creators_name: Martinez-Muriana, Anna creators_name: De Strooper, Bart creators_name: Thambisetty, Madhav creators_name: Ferrucci, Luigi creators_name: Gottesman, Rebecca F creators_name: Coresh, Josef creators_name: Resnick, Susan M creators_name: Walker, Keenan A title: Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: FD9 keywords: Alzheimer’s disease, Amyloid-beta, Positron emission tomography, Proteomics note: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). abstract: While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study. Genetic variation that influenced plasma levels of CAT, CD36 and KRT19 predicted rates of Aβ accumulation, including causal relationships with Aβ PET levels identified with two-sample Mendelian randomization. In addition to associations with tau PET and plasma AD biomarker changes, as well as expression patterns in human microglia subtypes and neurovascular cells in AD brain tissue, we showed that 31 % of candidate proteins were related to mid-life (20-year) or late-life (8-year) dementia risk in ARIC. Our findings reveal plasma proteins associated with longitudinal Aβ accumulation, and identify specific peripheral immune mediators that may contribute to the progression of AD pathophysiology. date: 2024-08 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/j.bbi.2024.07.002 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2298056 doi: 10.1016/j.bbi.2024.07.002 medium: Print-Electronic pii: S0889-1591(24)00471-9 lyricists_name: De Strooper, Bart lyricists_id: BDEST57 actors_name: De Strooper, Bart actors_id: BDEST57 actors_role: owner full_text_status: public publication: Brain, Behavior, and Immunity volume: 120 pagerange: 604-619 event_location: Netherlands issn: 0889-1591 citation: Duggan, Michael R; Gomez, Gabriela T; Joynes, Cassandra M; Bilgel, Murat; Chen, Jingsha; Fattorelli, Nicola; Hohman, Timothy J; ... Walker, Keenan A; + view all <#> Duggan, Michael R; Gomez, Gabriela T; Joynes, Cassandra M; Bilgel, Murat; Chen, Jingsha; Fattorelli, Nicola; Hohman, Timothy J; Mancuso, Renzo; Cordon, Jenifer; Castellano, Tonnar; Koran, Mary Ellen I; Candia, Julián; Lewis, Alexandria; Moghekar, Abhay; Ashton, Nicholas J; Kac, Przemysław R; Karikari, Thomas K; Blennow, Kaj; Zetterberg, Henrik; Martinez-Muriana, Anna; De Strooper, Bart; Thambisetty, Madhav; Ferrucci, Luigi; Gottesman, Rebecca F; Coresh, Josef; Resnick, Susan M; Walker, Keenan A; - view fewer <#> (2024) Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression. Brain, Behavior, and Immunity , 120 pp. 604-619. 10.1016/j.bbi.2024.07.002 <https://doi.org/10.1016/j.bbi.2024.07.002>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10194799/2/De%20Strooper_1-s2.0-S0889159124004719-main.pdf