TY - JOUR
T1 - Axonal damage and inflammation response are biological correlates of decline in small-world values
T2 - a cohort study in autosomal dominant Alzheimer’s disease
AU - on behalf of the Dominantly Inherited Alzheimer Network
AU - Vermunt, Lisa
AU - Sutphen, Courtney L.
AU - Dicks, Ellen
AU - de Leeuw, Diederick M.
AU - Allegri, Ricardo F.
AU - Berman, Sarah B.
AU - Cash, David M.
AU - Chhatwal, Jasmeer P.
AU - Cruchaga, Carlos
AU - Day, Gregory S.
AU - Ewers, Michael
AU - Farlow, Martin R.
AU - Fox, Nick C.
AU - Ghetti, Bernardino
AU - Graff-Radford, Neill R.
AU - Hassenstab, Jason
AU - Jucker, Mathias
AU - Karch, Celeste M.
AU - Kuhle, Jens
AU - Laske, Christoph
AU - Levin, Johannes
AU - Masters, Colin L.
AU - McDade, Eric
AU - Mori, Hiroshi
AU - Morris, John C.
AU - Perrin, Richard J.
AU - Preische, Oliver
AU - Schofield, Peter R.
AU - Suárez-Calvet, Marc
AU - Xiong, Chengjie
AU - Scheltens, Philip
AU - Teunissen, Charlotte E.
AU - Visser, Pieter Jelle
AU - Bateman, Randall J.
AU - Benzinger, Tammie L.S.
AU - Fagan, Anne M.
AU - Gordon, Brian A.
AU - Tijms, Betty M.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer’s disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer’s disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers (N = 219) and non-carriers (N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.
AB - The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer’s disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer’s disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers (N = 219) and non-carriers (N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.
KW - autosomal dominant Alzheimer disease
KW - axonal damage
KW - inflammation
KW - neuronal injury
KW - structural covariance network
UR - http://www.scopus.com/inward/record.url?scp=85208247642&partnerID=8YFLogxK
U2 - 10.1093/braincomms/fcae357
DO - 10.1093/braincomms/fcae357
M3 - Article
C2 - 39440304
AN - SCOPUS:85208247642
SN - 2632-1297
VL - 6
JO - Brain Communications
JF - Brain Communications
IS - 5
M1 - fcae357
ER -