scholarly journals Cerebral atherosclerosis contributes to Alzheimer’s dementia independently of its hallmark amyloid and tau pathologies

2019 ◽  
Author(s):  
Aliza P. Wingo ◽  
Wen Fan ◽  
Duc M. Duong ◽  
Ekaterina S. Gerasimov ◽  
Eric B. Dammer ◽  
...  
Keyword(s):  
Human Brain ◽  
Rna Splicing ◽  
Large Scale ◽  
Enrichment Analysis ◽  
Neurofilament Light ◽  
Synaptic Signaling ◽  
Cerebral Atherosclerosis ◽  
Dementia Risk ◽  
Brain Proteome ◽  
Oligodendrocyte Development

AbstractCerebral atherosclerosis is a leading cause of stroke and an important contributor to dementia. However, little is known about its molecular effects on the human brain and how these alterations may contribute to dementia. Here, we investigated these questions using large-scale quantification of over 8300 proteins from 438 post-mortem brains from a discovery and replication cohort. A proteome-wide association study and protein network analysis of cerebral atherosclerosis found 114 proteins and 5 protein co-expression modules associated with cerebral atherosclerosis. Enrichment analysis of these proteins and modules revealed that cerebral atherosclerosis was associated with reductions in synaptic signaling and RNA splicing and increases in oligodendrocyte development and myelination. A subset of these proteins (n=23) and protein modules (n=2) were also associated with Alzheimer’s disease (AD) dementia, implicating a shared mechanism with AD through decreased synaptic signaling and regulation and increased myelination. Notably, neurofilament light (NEFL) and medium (NEFM) chain proteins were among these 23 proteins, and our data suggest they contribute to AD dementia through cerebral atherosclerosis. Together, our findings offer insights into effects of cerebral atherosclerosis on the human brain proteome, and how cerebral atherosclerosis contributes to dementia risk.

Fundamental study on clarification of brain molecular pathology of Nasu-Hakola disease

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 24-26
Author(s):  
Jun-ichi Satoh
Keyword(s):  
Multiple Sclerosis ◽  
Human Brain ◽  
Clinical Research ◽  
Neurodegenerative Diseases ◽  
Molecular Pathology ◽  
Large Scale ◽  
Molecular Pathogenesis ◽  
Novel Therapies ◽  
Brain Pathology ◽  
Fundamental Study

Brain pathology expert Dr Jun-ichi Satoh, from the Department of Bioinformatics and Molecular Neuropathology of Meiji Pharmaceutical University in Tokyo, is drawing on his expertise on neurology and neuroimmunology to delve into some of the more complex diseases impacting the human brain. His knowledge and expertise have allowed him to direct his research interests to study neurodegenerative diseases, such as Alzheimer's disease (AD), and neuroinflammatory diseases, such as multiple sclerosis (MS), and the analysis of their molecular pathogenesis by using a bioinformatics approach. His current focus is on Nasu-Hakola disease (NHD), a disease whose rarity has posed significant barriers towards performing large-scale clinical research in order to understand what exactly causes this disease and develop effective novel therapies.

Human brain proteome in health and disease

2016 ◽  
Vol 10 (12) ◽  
pp. 1147-1147 ◽  
Author(s):  
Renã A. S. Robinson ◽  
Melanie Föcking ◽  
Daniel Martins-de-Souza
Keyword(s):  
Human Brain ◽  
Brain Proteome ◽  
Health And Disease

A Proteome-Wide Association Study Identified Candidate Human Brain Proteins Associated with Coffee Consumption

2021 ◽  
Author(s):  
Chun'e Li ◽  
Xiao Liang ◽  
Yumeng Jia ◽  
Yan Wen ◽  
Huijie Zhang ◽  
...  
Keyword(s):  
Human Brain ◽  
Association Study ◽  
Plasma Proteins ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Coffee Consumption ◽  
Genetic Associations ◽  
Brain Proteins ◽  
Genome Wide ◽  
Brain Proteome

Abstract Background Increasing evidence suggests the association between caffeine and the brain and nervous system. However, there is limited research on the genetic associations between coffee consumption subtypes and brain proteome, plasma proteomes, and peripheral metabolites. Methods First, proteome-wide association study (PWAS) of coffee consumption subtypes was performed by integrating two independent genome-wide association study (GWAS) datasets (91,462–502,650 subjects) with two reference human brain proteomes (ROS/MAP and Banner), by using the FUSION pipeline. Second, transcriptome-wide association study (TWAS) analysis of coffee consumption subtypes was conducted by integrating the two gene expression weight references (RNAseq and splicing) of brain RNA-seq and the two GWAS datasets (91,462–502,650 subjects) of coffee consumption subtypes. Finally, we used the LD Score Regression (LDSC) analysis to evaluate the genetic correlations of coffee consumption subtypes with plasma proteomes and peripheral metabolites. Results For the traits related to coffee consumption, we identified 3 common PWAS proteins, such as MADD (P PWAS−Banner−dis=0.0114, P PWAS−ROS/MAP−rep =0.0489). In addition, 11 common TWAS genes were found in two cohorts, such as ARPC2 (P TWAS−splicing−dis =2063×10− 12, P TWAS−splicing−dis =1.25×10− 10, P TWAS−splicing−dis =1.24e-08, P TWAS−splicing−rep =3.25×10− 9 and P TWAS−splicing−rep =3.42×10− 13). Importantly, we have identified 8 common genes between PWAS and TWAS, such as ALDH2 (P PWAS−banner−rep =1.22×10− 22, PTWAS− splicing−dis = 4.54×10− 92). For the LDSC analysis of human plasma proteome, we identified 11 plasma proteins, such as CHL1 (P dis = 0.0151, P rep =0.0438). For the LDSC analysis of blood metabolites, 5 metabolites have been found, such as myo-inositol (P dis = 0.0073, P dis = 0.0152, P dis =0.0414, P rep =0.0216). Conclusions We identified several brain proteins and genes associated with coffee consumption subtypes. In addition, we also detected several candidate plasma proteins and metabolites related to these subtypes.

scholarly journals Network dynamics with BrainX3: a large-scale simulation of the human brain network with real-time interaction

2015 ◽  
Vol 9 ◽  
Author(s):  
Xerxes D. Arsiwalla ◽  
Riccardo Zucca ◽  
Alberto Betella ◽  
Enrique Martinez ◽  
David Dalmazzo ◽  
...  
Keyword(s):  
Human Brain ◽  
Real Time ◽  
Large Scale ◽  
Network Dynamics ◽  
Brain Network ◽  
Large Scale Simulation ◽  
Time Interaction

scholarly journals Amplification and Suppression of Distinct Brain-wide Activity Patterns by Catecholamines

2018 ◽  
Author(s):  
RL van den Brink ◽  
S Nieuwenhuis ◽  
TH Donner
Keyword(s):  
Spatial Distribution ◽  
Human Brain ◽  
Spatial Patterns ◽  
Large Scale ◽  
Network Dynamics ◽  
Brain Network ◽  
Heterogeneous Distribution ◽  
Neurotransmitter Systems ◽  
The Brain ◽  
Catecholamine Levels

ABSTRACTThe widely projecting catecholaminergic (norepinephrine and dopamine) neurotransmitter systems profoundly shape the state of neuronal networks in the forebrain. Current models posit that the effects of catecholaminergic modulation on network dynamics are homogenous across the brain. However, the brain is equipped with a variety of catecholamine receptors with distinct functional effects and heterogeneous density across brain regions. Consequently, catecholaminergic effects on brain-wide network dynamics might be more spatially specific than assumed. We tested this idea through the analysis of functional magnetic resonance imaging (fMRI) measurements performed in humans (19 females, 5 males) at ‘rest’ under pharmacological (atomoxetine-induced) elevation of catecholamine levels. We used a linear decomposition technique to identify spatial patterns of correlated fMRI signal fluctuations that were either increased or decreased by atomoxetine. This yielded two distinct spatial patterns, each expressing reliable and specific drug effects. The spatial structure of both fluctuation patterns resembled the spatial distribution of the expression of catecholamine receptor genes: α1 norepinephrine receptors (for the fluctuation pattern: placebo > atomoxetine), ‘D2-like’ dopamine receptors (pattern: atomoxetine > placebo), and β norepinephrine receptors (for both patterns, with correlations of opposite sign). We conclude that catecholaminergic effects on the forebrain are spatially more structured than traditionally assumed and at least in part explained by the heterogeneous distribution of various catecholamine receptors. Our findings link catecholaminergic effects on large-scale brain networks to low-level characteristics of the underlying neurotransmitter systems. They also provide key constraints for the development of realistic models of neuromodulatory effects on large-scale brain network dynamics.SIGNIFICANCE STATEMENTThe catecholamines norepinephrine and dopamine are an important class of modulatory neurotransmitters. Because of the widespread and diffuse release of these neuromodulators, it has commonly been assumed that their effects on neural interactions are homogenous across the brain. Here, we present results from the human brain that challenge this view. We pharmacologically increased catecholamine levels and imaged the effects on the spontaneous covariations between brain-wide fMRI signals at ‘rest’. We identified two distinct spatial patterns of covariations: one that was amplified and another that was suppressed by catecholamines. Each pattern was associated with the heterogeneous spatial distribution of the expression of distinct catecholamine receptor genes. Our results provide novel insights into the catecholaminergic modulation of large-scale human brain dynamics.

scholarly journals Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort

2021 ◽  
Author(s):  
Tuulia Malén ◽  
Tomi Karjalainen ◽  
Janne Isojärvi ◽  
Aki Vehtari ◽  
Paul-Christian Bürkner ◽  
...  
Keyword(s):  
Human Brain ◽  
Large Scale ◽  
Movement Control ◽  
Heterogeneous Data ◽  
Small Sample ◽  
Cross Sectional ◽  
Psychiatric Conditions ◽  
Small Sample Sizes ◽  
Age And Sex

BACKGROUND: The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODS: In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTS: Striatal D2R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONS: D2R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.

scholarly journals Comparing the temporal relationship of structural and functional connectivity changes in different adult human brain networks: a single-case study

2018 ◽  
Vol 3 ◽  
pp. 50 ◽  
Author(s):  
Takamitsu Watanabe ◽  
Geraint Rees
Keyword(s):  
Functional Connectivity ◽  
Human Brain ◽  
Large Scale ◽  
Single Case ◽  
Brain Networks ◽  
Structural Connectivity ◽  
Time Lags ◽  
Single Case Study ◽  
Adult Human

Background: Despite accumulated evidence for adult brain plasticity, the temporal relationships between large-scale functional and structural connectivity changes in human brain networks remain unclear. Methods: By analysing a unique richly detailed 19-week longitudinal neuroimaging dataset, we tested whether macroscopic functional connectivity changes lead to the corresponding structural alterations in the adult human brain, and examined whether such time lags between functional and structural connectivity changes are affected by functional differences between different large-scale brain networks. Results: In this single-case study, we report that, compared to attention-related networks, functional connectivity changes in default-mode, fronto-parietal, and sensory-related networks occurred in advance of modulations of the corresponding structural connectivity with significantly longer time lags. In particular, the longest time lags were observed in sensory-related networks. In contrast, such significant temporal differences in connectivity change were not seen in comparisons between anatomically categorised different brain areas, such as frontal and occipital lobes. These observations survived even after multiple validation analyses using different connectivity definitions or using parts of the datasets. Conclusions: Although the current findings should be examined in independent datasets with different demographic background and by experimental manipulation, this single-case study indicates the possibility that plasticity of macroscopic brain networks could be affected by cognitive and perceptual functions implemented in the networks, and implies a hierarchy in the plasticity of functionally different brain systems.

scholarly journals Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ruedeerat Keerativittayayut ◽  
Ryuta Aoki ◽  
Mitra Taghizadeh Sarabi ◽  
Koji Jimura ◽  
Kiyoshi Nakahara
Keyword(s):  
Functional Connectivity ◽  
Human Brain ◽  
Large Scale ◽  
Brain Regions ◽  
Brain Network ◽  
Time Varying ◽  
Memory Encoding ◽  
Graph Metrics ◽  
Connectivity Patterns ◽  
Network States

Although activation/deactivation of specific brain regions has been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here, we investigated time-varying functional connectivity patterns across the human brain in periods of 30–40 s, which have recently been implicated in various cognitive functions. During functional magnetic resonance imaging, participants performed a memory encoding task, and their performance was assessed with a subsequent surprise memory test. A graph analysis of functional connectivity patterns revealed that increased integration of the subcortical, default-mode, salience, and visual subnetworks with other subnetworks is a hallmark of successful memory encoding. Moreover, multivariate analysis using the graph metrics of integration reliably classified the brain network states into the period of high (vs. low) memory encoding performance. Our findings suggest that a diverse set of brain systems dynamically interact to support successful memory encoding.

The Power of Poetry

2021 ◽  
pp. 182-187
Author(s):  
Eugen Wassiliwizky ◽  
Winfried Menninghaus
Keyword(s):  
Human Brain ◽  
Experimental Psychology ◽  
Large Scale ◽  
Multidisciplinary Approach ◽  
Scientific Investigation ◽  
Poetic Language ◽  
Social And Emotional ◽  
Parent Child Interactions ◽  
The Brain ◽  
Parent Child

From prehistory onward, poetic language has been widely used in the context of great personal, social, and emotional significance, reaching from large scale events, such as religious ceremonies, political occasions (including inaugurations of American presidents), and artistic contexts to more private gatherings, such as birthday parties, declarations of love, and parent–child interactions. Poetic language is capable of reaching deeply into the phylogenetically ancient structures of the human brain and providing profound aesthetic pleasures to its recipients. Yet a thorough scientific investigation of the workings of poetic language in the brain is only at its very beginnings. In the article under discussion, the authors review a study that focused on the emotional power of poetic language. In this project, they strived to integrate and interrelate perspectives from experimental psychology, neuroscience, rhetoric/poetics, psychophysiology, and philosophy. They argue that such a multidisciplinary approach is key to unraveling the mysteries of human aesthetic processing.

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