Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly
Open accessAbstract
Background Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. Methods Participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition. Results Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group. Conclusions Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Abeta toxicity can be detected using resting state fMRI.
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Some preclinical AD data has indicated altered rsfMRI FC resulting in a loss of connectivity in the default mode network and salience network, and this finding correlates with Aβ plaque accumulation, resulting in decreased connectivity between the precuneus and hippocampus.
“Some preclinical AD data has indicated altered rsfMRI FC (Sheline and Raichle, 2013) resulting in a loss of connectivity in the default mode network and salience network (Brier et al., 2012) and this finding correlates with Aβ plaque accumulation, resulting in decreased connectivity between the precuneus and hippocampus (Sheline et al., 2010).”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Sheline et al., 2010
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- Authors
- Sheline, Y. I., Raichle, M. E., Snyder, A. Z., Morris, J. C., Head, D., Wang, S., & Mintun, M. A.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 67
- Issue
- 6
- Pages
- 584-587
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2829379
- OpenAlex
- W2002610924
- Cited by
- 597
- References
- 5
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 27 · 2023: 31 · 2022: 25 · 2021: 31 · 2020: 33 · 2019: 46 · 2018: 34 · 2017: 45 · 2016: 45 · 2015: 35 · 2014: 46 · 2013: 41 · 2012: 46
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (K24MHO79510, P01AG026275, P01AG03991, P30NS048056, P30NS06833, P50AG05681)
- 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 plaques, amyloid-beta, default mode network, resting-state functional connectivity, preclinical Alzheimer's disease, cognitively normal elderly, Pittsburgh compound B PET, precuneus, hippocampus, anterior cingulate cortex
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Nerve Net, Oxygen, Psychiatric Status Rating Scales, Rest, Statistics as Topic, Thiazoles, Geriatric Assessment, Amyloid beta-Peptides, Positron-Emission Tomography
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