The human connectome in Alzheimer disease — relationship to biomarkers and genetics

Yu, Meichen; Sporns, Olaf; Saykin, Andrew J.

doi:10.1038/s41582-021-00529-1

Cited by 114 publications

(62 citation statements)

References 281 publications

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“…The effect of amyloid-β along the Alzheimer’s disease continuum was investigated using the global coupling between structural and functional brain networks. Although there was no difference in group-level global SC-FC coupling between different patient cohorts, Aβ pathology had distinctive stage-specific effects on the global coupling, consistent with previous studies that have investigated the structural and functional brain networks of AD separately [ 11 ].…”

Section: Discussionsupporting

confidence: 86%

“…Accumulation of Aβ has been shown to be associated with structural changes in subcortical volumes, cortical thickness, and surface area measures in healthy controls (HC) and MCI patients [ 10 ]. On the other hand, Aβ and tau pathologies also affect the anatomical and functional connections of the whole brain (known as structural and functional brain networks, respectively) in a stage-dependent manner [ 11 ]. It is of note that previous studies have focused on investigating the effect of AD pathologies on the structural or functional brain network alone.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

et al. 2021

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Previous studies have demonstrated that the accumulation of amyloid-β (Aβ) pathologies has distinctive stage-specific effects on the structural and functional brain networks along the Alzheimer’s disease (AD) continuum. A more comprehensive account of both types of brain network may provide a better characterization of the stage-specific effects of Aβ pathologies. A potential candidate for this joint characterization is the coupling between the structural and functional brain networks (SC-FC coupling). We therefore investigated the effect of Aβ accumulation on global SC-FC coupling in patients with mild cognitive impairment (MCI), AD, and healthy controls. Patients with MCI were dichotomized according to their level of Aβ pathology seen in 18F-flutemetamol PET-CT scans—namely, Aβ-negative and Aβ-positive. Our results show that there was no difference in global SC-FC coupling between different cohorts. During the prodromal AD stage, there was a significant negative correlation between the level of Aβ pathology and the global SC-FC coupling of MCI patients with positive Aβ, but no significant correlation for MCI patients with negative Aβ. During the AD dementia stage, the correlation between Aβ pathology and global SC-FC coupling in patients with AD was positive. Our results suggest that Aβ pathology has distinctive stage-specific effects on global coupling between the structural and functional brain networks along the AD continuum.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

et al. 2021

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“…Converging evidence indicates that Aβ initially accumulates in the medial frontal cortex and medial parietal cortex, which are both elements of the default-mode network (DMN). In contrast, tau is initially deposited in the medial temporal lobe memory system, spreading from the entorhinal cortex to the hippocampus and parahippocampal cortex, and then to other brain regions [ 75 , 76 ]. Insufficient mitochondrial function and bioenergy output of mitochondrial in AD patients may lead to a reduction in cellular energy levels, concomitant leakage of electrons promotes the formation of reactive oxygen species (ROS), which can damage proteins, membrane lipids and nucleic acids.…”

Section: Mitophagy In Chronic Diseases Of the Nervous Systemmentioning

confidence: 99%

Mitophagy in neurological disorders

Zhang

Dai

2021

J Neuroinflammation

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Selective autophagy is an evolutionarily conserved mechanism that removes excess protein aggregates and damaged intracellular components. Most eukaryotic cells, including neurons, rely on proficient mitophagy responses to fine-tune the mitochondrial number and preserve energy metabolism. In some circumstances (such as the presence of pathogenic protein oligopolymers and protein mutations), dysfunctional mitophagy leads to nerve degeneration, with age-dependent intracellular accumulation of protein aggregates and dysfunctional organelles, leading to neurodegenerative disease. However, when pathogenic protein oligopolymers, protein mutations, stress, or injury are present, mitophagy prevents the accumulation of damaged mitochondria. Accordingly, mitophagy mediates neuroprotective effects in some forms of neurodegenerative disease (e.g., Alzheimer's disease, Parkinson’s disease, Huntington's disease, and Amyotrophic lateral sclerosis) and acute brain damage (e.g., stroke, hypoxic–ischemic brain injury, epilepsy, and traumatic brain injury). The complex interplay between mitophagy and neurological disorders suggests that targeting mitophagy might be applicable for the treatment of neurodegenerative diseases and acute brain injury. However, due to the complexity of the mitophagy mechanism, mitophagy can be both harmful and beneficial, and future efforts should focus on maximizing its benefits. Here, we discuss the impact of mitophagy on neurological disorders, emphasizing the contrast between the positive and negative effects of mitophagy.

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“…Subsequently, further characterization of longitudinal misfolded protein spreading was also associated with regional expression levels of CLU (Sepulcre et al, 2018). a recent review summarized these findings and other connectomics related studies (Yu et al, 2021).…”

Section: Introductionmentioning

confidence: 89%

Relating Global and Local Connectome Changes to Dementia and Targeted Gene Expression in Alzheimer's Disease

Elsheikh

Chimusa

Initiative³

et al. 2021

Front. Hum. Neurosci.

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Networks are present in many aspects of our lives, and networks in neuroscience have recently gained much attention leading to novel representations of brain connectivity. The integration of neuroimaging characteristics and genetics data allows a better understanding of the effects of the gene expression on brain structural and functional connections. The current work uses whole-brain tractography in a longitudinal setting, and by measuring the brain structural connectivity changes studies the neurodegeneration of Alzheimer's disease. This is accomplished by examining the effect of targeted genetic risk factors on the most common local and global brain connectivity measures. Furthermore, we examined the extent to which Clinical Dementia Rating relates to brain connections longitudinally, as well as to gene expression. For instance, here we show that the expression of PLAU gene increases the change over time in betweenness centrality related to the fusiform gyrus. We also show that the betweenness centrality metric impact dementia-related changes in distinct brain regions. Our findings provide insights into the complex longitudinal interplay between genetics and brain characteristics and highlight the role of Alzheimer's genetic risk factors in the estimation of regional brain connectivity alterations.

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The human connectome in Alzheimer disease — relationship to biomarkers and genetics

Cited by 114 publications

References 281 publications

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Mitophagy in neurological disorders

Relating Global and Local Connectome Changes to Dementia and Targeted Gene Expression in Alzheimer's Disease

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