Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease

Lisa Vermunt; Courtney L Sutphen; Ellen Dicks; Diederick M de Leeuw; Ricardo F Allegri; Sarah B Berman; David M Cash; Jasmeer P Chhatwal; Carlos Cruchaga; Gregory S Day; Michael Ewers; Martin R Farlow; Nick C Fox; Bernardino Ghetti; Neill R Graff-Radford; Jason Hassenstab; Mathias Jucker; Celeste M Karch; Jens Kuhle; Christoph Laske; Johannes Levin; Colin L Masters; Eric McDade; Hiroshi Mori; John C Morris; Richard J Perrin; Oliver Preische; Peter R Schofield; Marc Suárez-Calvet; Chengjie Xiong; Philip Scheltens; Charlotte E Teunissen; Pieter Jelle Visser; Randall J Bateman; Tammie L S Benzinger; Anne M Fagan; Brian A Gordon; Betty M Tijms

doi:10.1093/braincomms/fcae357

Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease

Lisa Vermunt^*, Courtney L Sutphen, Ellen Dicks, Diederick M de Leeuw^*, Ricardo F Allegri, Sarah B Berman, David M Cash, Jasmeer P Chhatwal, Carlos Cruchaga, Gregory S Day, Michael Ewers, Martin R Farlow, Nick C Fox, Bernardino Ghetti, Neill R Graff-Radford, Jason Hassenstab, Mathias Jucker, Celeste M Karch, Jens Kuhle, Christoph LaskeJohannes Levin, Colin L Masters, Eric McDade, Hiroshi Mori, John C Morris, Richard J Perrin, Oliver Preische, Peter R Schofield, Marc Suárez-Calvet, Chengjie Xiong, Philip Scheltens, Charlotte E Teunissen, Pieter Jelle Visser, Randall J Bateman, Tammie L S Benzinger, Anne M Fagan, Brian A Gordon, Betty M Tijms

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	fcae357
Number of pages	12
Journal	Brain Communications
Volume	6
Issue number	5
DOIs	https://doi.org/10.1093/braincomms/fcae357
Publication status	Published - 9 Oct 2024

Keywords

autosomal dominant Alzheimer disease
axonal damage
inflammation
neuronal injury
structural covariance network

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Vermunt, L., Sutphen, C. L., Dicks, E., de Leeuw, D. M., Allegri, R. F., Berman, S. B., Cash, D. M., Chhatwal, J. P., Cruchaga, C., Day, G. S., Ewers, M., Farlow, M. R., Fox, N. C., Ghetti, B., Graff-Radford, N. R., Hassenstab, J., Jucker, M., Karch, C. M., Kuhle, J., ... Tijms, B. M. (2024). Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease. Brain Communications, 6(5), Article fcae357. https://doi.org/10.1093/braincomms/fcae357

@article{3a124dfab3df4c12b2935ced1eea6510,

title = "Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease",

abstract = "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{\textquoteright}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{\textquoteright}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.",

keywords = "autosomal dominant Alzheimer disease, axonal damage, inflammation, neuronal injury, structural covariance network",

author = "Lisa Vermunt and Sutphen, {Courtney L} and Ellen Dicks and {de Leeuw}, {Diederick M} and Allegri, {Ricardo F} and Berman, {Sarah B} and Cash, {David M} and Chhatwal, {Jasmeer P} and Carlos Cruchaga and Day, {Gregory S} and Michael Ewers and Farlow, {Martin R} and Fox, {Nick C} and Bernardino Ghetti and Graff-Radford, {Neill R} and Jason Hassenstab and Mathias Jucker and Karch, {Celeste M} and Jens Kuhle and Christoph Laske and Johannes Levin and Masters, {Colin L} and Eric McDade and Hiroshi Mori and Morris, {John C} and Perrin, {Richard J} and Oliver Preische and Schofield, {Peter R} and Marc Su{\'a}rez-Calvet and Chengjie Xiong and Philip Scheltens and Teunissen, {Charlotte E} and Visser, {Pieter Jelle} and Bateman, {Randall J} and Benzinger, {Tammie L S} and Fagan, {Anne M} and Gordon, {Brian A} and Tijms, {Betty M}",

year = "2024",

month = oct,

day = "9",

doi = "10.1093/braincomms/fcae357",

language = "English",

volume = "6",

journal = "Brain Communications",

issn = "2632-1297",

publisher = "Oxford University Press",

number = "5",

}

Vermunt, L, Sutphen, CL, Dicks, E, de Leeuw, DM, Allegri, RF, Berman, SB, Cash, DM, Chhatwal, JP, Cruchaga, C, Day, GS, Ewers, M, Farlow, MR, Fox, NC, Ghetti, B, Graff-Radford, NR, Hassenstab, J, Jucker, M, Karch, CM, Kuhle, J, Laske, C, Levin, J, Masters, CL, McDade, E, Mori, H, Morris, JC, Perrin, RJ, Preische, O, Schofield, PR, Suárez-Calvet, M, Xiong, C, Scheltens, P, Teunissen, CE, Visser, PJ, Bateman, RJ, Benzinger, TLS, Fagan, AM, Gordon, BA & Tijms, BM 2024, 'Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease', Brain Communications, vol. 6, no. 5, fcae357. https://doi.org/10.1093/braincomms/fcae357

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 - 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

PY - 2024/10/9

Y1 - 2024/10/9

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

U2 - 10.1093/braincomms/fcae357

DO - 10.1093/braincomms/fcae357

M3 - Article

SN - 2632-1297

VL - 6

JO - Brain Communications

JF - Brain Communications

IS - 5

M1 - fcae357

ER -

Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease

Abstract

Keywords

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