Gray matter network disruptions and amyloid beta in cognitively normal adults
Abstract
Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aβ42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Aβ42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aβ42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p < 0.05). These results suggest that mostly within the normal spectrum of amyloid, lower Aβ42 levels can be related to gray matter networks disruptions.
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Lower CSF levels of amyloid-beta are associated with higher path length and lower clustering of the gray matter structural connectome in human participants.
“Lower cerebrospinal fluid (CSF) levels of amyloid-beta have been associated with higher path length and lower clustering of the gray matter structural connectome in human participants”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Tijms et al., 2015
Low levels of amyloid-beta in the CSF indicate higher amyloid plaque burden in the brain.
“low levels of amyloid-beta in the CSF indicate higher amyloid plaque burden in the brain (Tijms et al., 2015).”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Tijms et al., 2015
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Yu, M., Sporns, O., & Saykin, A. J. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00529-1 · Cited by 265 · see citing works
Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults
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“Lower cerebrospinal fluid (CSF) levels of amyloid-beta have been associated with higher path length and lower clustering of the gray matter structural connectome in human participants; low levels of amyloid-beta in the CSF indicate higher amyloid plaque burden in the brain (Tijms et al., 2015).”
Background
- Authors
- Tijms, B. M., Kate, M. T., Wink, A. M., Visser, P. J., Ecay, M., Clerigue, M., Estanga, A., Garcia Sebastian, M., Izagirre, A., Villanua, J., Martinez Lage, P., van der Flier, W. M., Scheltens, P., Sanz Arigita, E., & Barkhof, F.
- Affiliations
- Amsterdam Neuroscience (NL)
- Maastricht University (NL)
- Fundacion CITA Alzheimer (ES)
- Corresponding author
- Tijms, Betty M.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 37
- Pages
- 154-160
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2191660274
- Cited by
- 59
- References
- 10
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 10 · 2020: 4 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 5 · 2013: 1
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Basque Government (S-PR13ZH001)
- Instituto de Salud Carlos III (PI112-02262)
- Alzheimer Nederland and Stichting VUmc fonds
- EMIF (115372)
- European Union's Seventh Framework Programme
- EFPIA companies'
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyloid-beta 42, Alzheimer's disease, cerebrospinal fluid biomarkers, network connectivity, clustering coefficient, path length, medial temporal lobe, precuneus, middle frontal gyrus, cognitively normal adults, early Alzheimer's disease
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments, Amyloid beta-Peptides, Cognitive Reserve, Gray Matter
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