Telomeric alterations in the default mode network during the progression of Alzheimer’s disease: Selective vulnerability of the precuneus

Mahady, Laura; He, Bin; Malek-Ahmadi, Michael; Mufson, Elliott J.

doi:10.1111/nan.12672

Cited by 14 publications

(8 citation statements)

References 112 publications

(267 reference statements)

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“…Features of specific cells during AD exhibit features indicative of cells that undergoes senescence. For example, telomeric alterations and hyperproliferation-mediated DNA damage in cellular senescence have been observed in AD as well [ 52 ]. Particularly, one study demonstrated the correlation between AD and DNA double strand breaks where the authors have observed an increased γ-H2A.X (Ser139) positive neurons and GFAP positive astrocytes in the hippocampus of human AD postmortem brains compared to non-AD brains [ 53 ].…”

Section: The Role Of Ceramide In Ad Cell Linesmentioning

confidence: 99%

Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease

2022

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and is associated with several pathophysiological features, including cellular dysfunction, failure of neurotransmission, cognitive impairment, cell death, and other clinical consequences. Advanced research on the pathogenesis of AD has elucidated a mechanistic framework and revealed many therapeutic possibilities. Among the mechanisms, sphingolipids are mentioned as distinctive mediators to be associated with the pathology of AD. Reportedly, alteration in the metabolism of sphingolipids and their metabolites result in the dysfunction of mitochondria, autophagy, amyloid beta regulation, and neuronal homeostasis, which exacerbates AD progression. Considering the importance of sphingolipids, in this review, we discuss the role of ceramide, a bioactive sphingolipid metabolite, in the progression and pathogenesis of AD. Herein, we describe the ceramide synthesis pathway and its involvement in the dysregulation of homeostasis, which eventually leads to AD. Furthermore, this review references different therapeutics proposed to modulate the ceramide pathway to maintain ceramide levels and prevent the disease progression.

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Section: The Role Of Ceramide In Ad Cell Linesmentioning

confidence: 99%

Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease

2022

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“…It has also been found that patients with Alzheimer's disease (AD) and in the prodromal stage of AD have decreased DMN functions and precuneus GM volume compared to controls. Using post-mortem brains, a telomere length analysis of each brain region comprising the DMN showed that the precuneus telomere length was shorter in AD and prodromal stage of AD than in controls, whereas there were no differences in the frontal, inferior temporal, posterior cingulate gyrus or visual cortex [24]. Furthermore, this telomere length reduction in the precuneus was also correlated with cognitive task performance.…”

Section: Discussionmentioning

confidence: 96%

Epigenetic Clock Deceleration and Maternal Parity: Associations With Increasing Grey Matter Volume of the Precuneus

Nishitani¹,

Kasaba²,

Hiraoka³

et al. 2020

Preprint

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Reproductive effort experiences, such as pregnancy, delivery, and interaction with their children, make female maternal brains optimised for child-rearing. However, extensive studies in non-human species revealed there is a trade-off between reproductive effort and life expectancy. In humans, large demographic studies have shown that this is the case for the most part, but molecular marker studies of aging remain controversial, and there are no studies evaluating the relationship between reproductive effort, aging, and brain structures simultaneously. We examined the associations among the reproductive efforts, DNA methylation age acceleration, and the regional grey matter of structural brain scans by voxel-based morphometry in 27-46-year-old mothers. We found that greater reproductive efforts, including the number of delivery and motherhood periods, were significantly associated with decelerated aging in mothers with 1-4 children. We also found that the precuneus grey matter volume was larger as age deceleration occurred and found a mediation effect of the greater left precuneus grey matter volume on the relationship between parity and age deceleration. Our findings suggest that mothers of early childhood children who have less than four children may benefit from aging via precuneus structural changes.

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“…It has also been found that patients with Alzheimer’s disease (AD) and in the prodromal stage of AD have decreased DMN functions and precuneus GM volume compared to controls ( Goto et al, 2015 ). Using postmortem brains, a telomere length analysis of each brain region comprising the DMN showed that the precuneus telomere length was shorter in AD and the prodromal stage of AD than in controls, whereas there were no differences in the frontal, inferior temporal, posterior cingulate gyrus or visual cortex ( Mahady et al, 2020 ). Furthermore, this telomere length reduction in the precuneus also correlated with cognitive task performance.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Clock Deceleration and Maternal Reproductive Efforts: Associations With Increasing Gray Matter Volume of the Precuneus

et al. 2022

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Reproductive efforts, such as pregnancy, delivery, and interaction with children, make maternal brains optimized for child-rearing. However, extensive studies in non-human species revealed a tradeoff between reproductive effort and life expectancy. In humans, large demographic studies have shown that this is the case for the most part; however, molecular marker studies regarding aging remain controversial. There are no studies simultaneously evaluating the relationship between reproductive effort, aging, and brain structures. We therefore examined the associations between reproductive efforts (parity status, number of deliveries, motherhood period, and cumulative motherhood period), DNA methylation age (mAge) acceleration (based on Horvath’s multi-tissue clock and the skin & blood clock), and the regional gray matter volumes (obtained through brain magnetic resonance imaging (MRI) using voxel-based morphometry) in 51 mothers aged 27–46 years of children in early childhood. We found that increasing reproductive efforts were significantly associated with decelerated aging in mothers with one to four children, even after adjusting for the confounding effects in the multiple linear regression models. We also found that the left precuneus gray matter volume was larger as deceleration of aging occurred; increasing left precuneus gray matter volume, on the other hand, mediates the relationship between parity status and mAge deceleration. Our findings suggest that mothers of children in early childhood, who have had less than four children, may benefit from deceleration of aging mediated via structural changes in the precuneus.

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Telomeric alterations in the default mode network during the progression of Alzheimer’s disease: Selective vulnerability of the precuneus

Cited by 14 publications

References 112 publications

Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease

Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease

Epigenetic Clock Deceleration and Maternal Parity: Associations With Increasing Grey Matter Volume of the Precuneus

Epigenetic Clock Deceleration and Maternal Reproductive Efforts: Associations With Increasing Gray Matter Volume of the Precuneus

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