Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly
Yvette I. Sheline, Marcus E. Raichle, Abraham Z. Snyder, John C. Morris, Denise Head, Suzhi Wang, Mark A. Mintun
Biological Psychiatry October 15, 2009 DOI: 10.1016/j.biopsych.2009.08.024 via OpenAlex
Summary
AI-generated from the abstractFunctional connections within the default mode network are disrupted in Alzheimer's disease, likely due to amyloid-beta plaque toxicity. In cognitively normal participants with preclinical amyloid deposition, resting-state fMRI revealed differences in functional connectivity between the precuneus and several brain regions—including the hippocampus, parahippocampus, and cingulate cortex—that matched the pattern seen in Alzheimer's disease patients. These findings suggest that early amyloid-beta toxicity can be detected with resting-state fMRI before any cognitive or behavioral changes appear.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 103 |
| Population | Cognitively normal participants and Alzheimer's disease patients |
| Citations | 608 |
| Key finding | Cognitively normal participants with brain amyloid deposition showed altered resting-state functional connectivity in the same regions and direction as Alzheimer's disease patients. |
Abstract
BackgroundImportant 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.MethodsParticipants 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.ResultsResting 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.ConclusionsThus, 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.