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