Astrocytic Calcium and Default Mode Network Dysfunction in Early Stage AD
Denis Larrivee
Alzheimer's Disease - Diagnostics, Pathogenesis, and Treatment [Working Title] July 1, 2026 DOI: 10.5772/intechopen.1016224 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Default mode network |
| Key points | Argues that dysfunctional calcium signaling in astrocytes, rather than neurons, parallels early functional connectivity changes in the default mode network and may be a primary site of pathogenesis in early Alzheimer's disease. |
Abstract
While most theories regarding Alzheimer’s disease (AD) pathogenesis adopt a “neurocentric” perspective, increasing evidence suggests that nonneuronal cells may be a primary site of pathogenesis in early stage AD. Several years prior to the appearance of amyloid plaques and neurofibrillary tangles (NFTs), functional connectivity (FC) changes can be observed in the human cingulate cortex, a principal hub of the default mode network (DMN). Recent studies confirm the presence of dysfunctional calcium signaling in astrocytes, but not neurons, that parallels the observed changes in FC, whereas restoration of normal calcium reverses these changes. Significantly, astrocytes are known to be key elements of brain communication, supporting bidirectional information exchange with neurons at synaptic sites, directly engaging in synaptic transmission, and coordinating multisynaptic activity at circuit and network levels. They are also demonstrably circuit and network-specific. Given their intimate involvement in transmitting neural information, the study of calcium signaling in DMN astrocytes could yield key insights into early AD pathogenesis. Currently, there is a growing body of findings regarding the calcium signaling mechanisms used by astrocytes to initiate or respond to synaptic neural activity and an expanding arsenal of techniques that could provide insight into the systemic consequences of AD-related astrocyte failure. This chapter integrates methods and findings of connectivity disruption in the DMN with those of dysfunctional calcium signaling to provide a perspective on the growing technical synergy that could be used for assessing the influence of astrocytes in early AD pathogenesis.
Comparable studies
Other theoretical and historical papers on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs | 2014 | Theoretical or philosophical paper | |
| The default mode network in cognition: a topographical perspective | 2021 | Theoretical or philosophical paper | |
| The default mode network: where the idiosyncratic self meets the shared social world | 2021 | Theoretical or philosophical paper | |
| The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas | 2010 | Theoretical or philosophical paper | |
| Cooperation between the default mode network and the frontal–parietal network in the production of an internal train of thought | 2011 | Theoretical or philosophical paper |
Citations in the library
Cites 7
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Cerebral Cortex April 9, 2008
- 20 years of the default mode network: A review and synthesis Neuron May 10, 2023
- Mapping the self in the brain's default mode network Neuroimage February 15, 2016
- The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow Nature Neuroscience January 28, 2025
and 2 more in the library