scholarly journals Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer’s disease and longevity in an Italian population

GeroScience ◽  
2021 ◽  
Author(s):  
Maria Giulia Bacalini ◽  
Flavia Palombo ◽  
Paolo Garagnani ◽  
Cristina Giuliani ◽  
Claudio Fiorini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Successful Aging ◽  
Clock Genes ◽  
Association Studies ◽  
Italian Population ◽  
Age Related

AbstractMany physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.

The Rhythmicity of Clock Genes is Disrupted in the Choroid Plexus of the APP/PS1 Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 77 (2) ◽  
pp. 795-806 ◽  
Author(s):  
André Furtado ◽  
Rosario Astaburuaga ◽  
Ana Costa ◽  
Ana C. Duarte ◽  
Isabel Gonçalves ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Circadian Clock ◽  
Choroid Plexus ◽  
Clock Genes ◽  
Amyloid Β ◽  
Model Of Alzheimer’S Disease ◽  
Pre Treatment

Background: The choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, was recently identified as an important component of the circadian clock system. Objective: The fact that circadian rhythm disruption is closely associated to Alzheimer’s disease (AD) led us to investigate whether AD pathology can contribute to disturbances of the circadian clock in the CP. Methods: For this purpose, we evaluated the expression of core-clock genes at different time points, in 6- and 12-month-old female and male APP/PS1 mouse models of AD. In addition, we also assessed the effect of melatonin pre-treatment in vitro before amyloid-β stimulus in the daily pattern of brain and muscle Arnt-like protein 1 (Bmal1) expression. Results: Our results showed a dysregulation of circadian rhythmicity of Bmal1 expression in female and male APP/PS1 transgenic 12-month-old mice and of Period 2 (Per2) expression in male mice. In addition, a significant circadian pattern of Bmal1 was measured the intermittent melatonin pre-treatment group, showing that melatonin can reset the CP circadian clock. Conclusion: These results demonstrated a connection between AD and the disruption of circadian rhythm in the CP, representing an attractive target for disease prevention and/or treatment.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Fatin N. Zainul Abidin ◽  
Helena R. R. Wells ◽  
Andre Altmann ◽  
Sally J. Dawson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Correlation ◽  
Genetic Architecture ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Age Related ◽  
Hearing Difficulty ◽  
Shared Genetic

AbstractAge-related hearing loss was recently established as the largest modifiable risk factor for Alzheimer’s disease (AD), however, the reasons for this link remain unclear. We investigate shared underlying genetic associations using results from recent large genome-wide association studies (GWAS) on adult hearing difficulty and AD. Genetic correlation and Mendelian randomization (MR) analysis do not support a genetic correlation between the disorders, but suggest a direct causal link from AD genetic risk to hearing difficulty, driven by APOE. Systematic MR analyses on the effect of other traits revealed shared effects of glutamine, gamma-glutamylglutamine, and citrate levels on reduced risk of both hearing difficulty and AD. In addition, pathway analysis on GWAS risk variants suggests shared function in neuronal signalling pathways as well as etiology of diabetes and cardiovascular disease. However, after multiple testing corrections, neither analysis led to statistically significant associations. Altogether, our genetic-driven analysis suggests hearing difficulty and AD are linked by a shared vulnerability in molecular pathways rather than by a shared genetic architecture.

scholarly journals The Contribution of Epigenetic Inheritance Processes on Age-Related Cognitive Decline and Alzheimer’s Disease

Epigenomes ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 15
Author(s):  
Aina Bellver-Sanchis ◽  
Mercè Pallàs ◽  
Christian Griñán-Ferré
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Cognitive Decline ◽  
Association Studies ◽  
Cognitive Status ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Age Related Cognitive Decline

During the last years, epigenetic processes have emerged as important factors for many neurodegenerative diseases, such as Alzheimer’s disease (AD). These complex diseases seem to have a heritable component; however, genome-wide association studies failed to identify the genetic loci involved in the etiology. So, how can these changes be transmitted from one generation to the next? Answering this question would allow us to understand how the environment can affect human populations for multiple generations and explain the high prevalence of neurodegenerative diseases, such as AD. This review pays particular attention to the relationship among epigenetics, cognition, and neurodegeneration across generations, deepening the understanding of the relevance of heritability in neurodegenerative diseases. We highlight some recent examples of EI induced by experiences, focusing on their contribution of processes in learning and memory to point out new targets for therapeutic interventions. Here, we first describe the prominent role of epigenetic factors in memory processing. Then, we briefly discuss aspects of EI. Additionally, we summarize evidence of how epigenetic marks inherited by experience and/or environmental stimuli contribute to cognitive status offspring since better knowledge of EI can provide clues in the appearance and development of age-related cognitive decline and AD.

scholarly journals Functional biological paths altered in Alzheimer’s disease: from genes to bile acids

2020 ◽  
Author(s):  
Priyanka Gorijala ◽  
Kwangsik Nho ◽  
Shannon L. Risacher ◽  
Rima Kaddurah-Daouk ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bile Acids ◽  
Biological Networks ◽  
Large Scale ◽  
Association Studies ◽  
Underlying Mechanism ◽  
Genome Wide Association Studies ◽  
Functional Protein ◽  
Age Related

AbstractLarge-scale genome wide association studies (GWASs) have been performed in search for risk genes for Alzheimer’s disease (AD). Despite the significant progress, replicability of genetic findings and their translation into targetable mechanisms related to the disease pathogenesis remains a challenge. Given that bile acids have been suggested in recent metabolic studies as potential age-related metabolic factors associated with AD, we integrated genomic and metabolomic data together with heterogeneous biological networks and investigated the potential cascade of effect of genetic variations to proteins, bile acids and ultimately AD brain phenotypes. Particularly, we leveraged functional protein interaction networks and metabolic networks and focused on the genes directly interacting with AD-altered bile acids and their functional regulators. We examined the association of all the SNPs located in those candidate genes with AD brain imaging phenotypes, and identified multiple AD risk SNPs whose downstream genes and bile acids were also found to be altered in AD. These AD related markers span from genetics to metabolomics, forming functional biological paths connecting across multiple-omics layers, and give valuable insights into the underlying mechanism of AD.

scholarly journals A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease

2022 ◽  
Vol 23 (1) ◽  
pp. 504
Author(s):  
Xuemin Peng ◽  
Rongping Fan ◽  
Lei Xie ◽  
Xiaoli Shi ◽  
Kun Dong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Light Therapy

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

scholarly journals Simulated Space Environmental Factors of Weightlessness, Noise and Low Air Pressure Differentially Affect the Circadian Rhythm and Gut Microbiome

2021 ◽  
Author(s):  
Huan Ma ◽  
Xihui Gan ◽  
Jianwei Zhao ◽  
Yin Zhang ◽  
Silin Li ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Community Structure ◽  
Circadian Rhythms ◽  
Environmental Factors ◽  
Circadian Clock ◽  
Gut Microbiome ◽  
Atmospheric Pressure ◽  
Clock Genes ◽  
Low Atmospheric Pressure ◽  
Space Capsule

Abstract Backgroundhe circadian clock extensively regulates physiology and behavior. In space, the astronauts encounter many environmental factors that are dramatically different from those on earth, however, the effects of these factors on circadian rhythms and the mechanisms remain largely unknown. The present study aimed to investigate the changes in the mouse circadian rhythm and gut microbiome under simulated space capsule conditions, including microgravity, noise and low atmospheric pressure.ResultsNoise and low atmospheric pressure were loaded in the capsule while the conditions in the animal room remained constant. The mice in the capsule showed disturbed locomotor rhythms and faster adaptation to a 6-h phase advance. RNA sequencing of hypothalamus samples revealed that microgravity simulated by hind limb unloading (HU) and exposure to noise and low atmospheric pressure led to decreases in the quantities of differentially expressed genes (DEGs), including circadian clock genes. Changes in the rhythmicity of genes implicated in pathways of cardiovascular deconditioning and more concentrated circadian phases were found under HU or noise and low atmospheric pressure. Furthermore, 16S rRNA sequencing revealed dysbiosis in the gut microbiome, and noise and low atmospheric pressure may repress the temporal discrepancy in the microbiome community structure induced by microgravity. Changes in diel oscillation were observed in a number of gut bacteria with critical physiological consequences in metabolism and immunodefense.ConclusionsOur data demonstrate that in addition to microgravity, exposure to noise and low atmospheric pressure affect the robustness of circadian rhythms and the community structure of the gut microbiome, and these factors may interfere with each other in their adaptation to respective conditions. These findings are important to further our understanding of the alteration of circadian rhythms in the space complex environment.

scholarly journals Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer’s disease in comparison with healthy aging

GeroScience ◽  
2020 ◽  
Author(s):  
Maria Conte ◽  
Jacopo Sabbatinelli ◽  
Antonio Chiariello ◽  
Morena Martucci ◽  
Aurelia Santoro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Levels ◽  
Successful Aging ◽  
Healthy Aging ◽  
Fibroblast Growth Factor 21 ◽  
Age Related ◽  
Health And Disease ◽  
Disease Specificity

Abstract Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diabetes (T2D) or Alzheimer’s disease (AD), two age-related diseases sharing a mitochondrial impairment, we found that GDF15 is elevated in T2D but not in AD and represents a risk factor for T2D complications, while FGF21 and HN are lower in AD but not in T2D. Moreover, FGF21 reaches the highest levels in centenarian’ offspring, a model of successful aging. As a whole, these data indicate that (i) the adaptive mitokine response observed in healthy aging is lost in age-related diseases, (ii) a common expression pattern of mitokines does not emerge in T2D and AD, suggesting an unpredicted complexity and disease-specificity, and (iii) FGF21 emerges as a candidate marker of healthy aging.

Circadian Rhythm-Related Behavioral Disturbances and Structural Hypothalamic Changes in Alzheimer's Disease

1997 ◽  
Vol 8 (S3) ◽  
pp. 245-252 ◽  
Author(s):  
Witte J. G. Hoogendijk ◽  
Eus J. W. van Someren ◽  
Majid Mirmiran ◽  
Michel A. Hofman ◽  
Paul J. Lucassen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Older Persons ◽  
Behavioral Disturbances ◽  
Age Related ◽  
Wake Patterns ◽  
Nocturnal Restlessness ◽  
Mental Decline ◽  
Age Related Changes

Age-related changes in circadian rhythm (e.g., fragmented sleep-wake patterns) occur in many older persons but are particularly pronounced in patients with Alzheimer's disease. In these patients, disruptions of circadian rhythms can be severe enough to increase mental decline, agitation during the day, and restlessness at night. Moreover, patients whose nocturnal restlessness disrupts the sleep of the caregiver are more likely to be institutionalized than those who have cognitive impairment alone.

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