Leonidas Chouliaras

University of Cambridge

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

John T. O’Brien

Bedford Institute of Oceanography

James B. Rowe

MRC Cognition and Brain Sciences Unit

Maura Malpetti

University of Cambridge

Bart P. F. Rutten

Maastricht University Medical Centre

George Savulich

University of Cambridge

Daniël van den Hove

Maastricht University

Peter G. Swann

University of Cambridge

Harry W.M. Steinbusch

Maastricht University

Elijah Mak

University of Cambridge

Günter Kenis

European Graduate School of Neuroscience

Cooperative Institutions

University of Cambridge

University College London

Instituto de Salud Carlos III

Maastricht University

Centro de Investigación Biomédica en Red

European Graduate School of Neuroscience

Cambridge University Hospitals NHS Foundation Trust

University of Oxford

King's College London

Maastricht University Medical Centre

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid‐positive mild cognitive impairment is associated with key clinical features

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring (2019)

Audrey Low Elijah Mak Maura Malpetti Leonidas Chouliaras Nicolas Nicastro

Although widespread cortical asymmetries have been identified in Alzheimer's disease (AD), thalamic asymmetries and their relevance to clinical severity in AD remain unclear.Lateralization indices were computed for individual thalamic subnuclei of 65 participants (33 healthy controls, 14 amyloid-positive patients with mild cognitive impairment, and 18 patients with AD dementia). We compared lateralization indices across diagnostic groups and correlated them with clinical measures.Although overall asymmetry of the thalamus did not differ between groups, greater leftward lateralization of atrophy in the ventral nuclei was demonstrated in AD, compared with controls and amyloid-positive mild cognitive impairment. Increased posterior ventrolateral and ventromedial nuclei asymmetry were associated with worse cognitive dysfunction, informant-reported neuropsychiatric symptoms, and functional ability.Leftward ventral thalamic atrophy was associated with disease severity in AD. Our findings suggest the clinically relevant involvement of thalamic nuclei in the pathophysiology of AD.

10.1016/j.dadm.2019.08.001

Cite

Citations (36)

Histone Deacetylase 2 in the Mouse Hippocampus: Attenuation of Age- Related Increase by Caloric Restriction

Current Alzheimer Research (2013)

Leonidas Chouliaras Daniël van den Hove Günter Kenis Michael Draanen Patrick R. Hof

The aging process in the hippocampus is associated with aberrant epigenetic marks, such as DNA methylation and histone tail alterations. Recent evidence suggests that caloric restriction (CR) can potentially delay the aging process, while upregulation of antioxidants may also have a beneficial effect in this respect. We have recently observed that CR attenuates age-related changes in the levels of the epigenetic molecules DNA methyltransferase 3a, 5-methylcytidine (5- mC) and 5-hydroxymethylcytosine in the mouse hippocampus while overexpression of the antioxidant Cu/Zn superoxide dismutase 1 (SOD1) does not. However, the impact of aging on the levels of histone-modifying enzymes such as histone deacetylase 2 (HDAC2) in the hippocampus has not been studied in much detail. Here, we investigated immunoreactivity (IR) of HDAC2 in three subregions of the hippocampus (dentate gyrus, CA3 and CA1-2) of mice taken from large cohorts of aging wild-type and transgenic mice overexpressing normal human SOD1, which were kept under normal diet or CR from weaning onwards. Independent from the genotype, aging (between 12 and 24 months) increased levels of HDAC2 IR in the hippocampus. Moreover, CR prevented this age-related increase, particularly in the CA3 and CA1-2 subregions, while SOD1 overexpression did not. Quantitative image analyses showed that HDAC2 IR correlated positively with 5-mC IR while these markers were shown to colocalize in the nucleus of hippocampal cells. Together with recent literature reports, these findings suggest that altered levels of epigenetic regulatory proteins including HDAC2 regulate age-related changes in the mouse hippocampus and that CR may prevent these age-related changes.

Histone deacetylase 2

10.2174/1567205011310080009

Cite

Citations (51)

Considering the senses in the diagnosis and management of dementia

Maturitas (2014)

Sophie Behrman Leonidas Chouliaras Klaus P. Ebmeier

10.1016/j.maturitas.2014.01.003

Cite

Citations (65)

Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in mouse hippocampus

Brain Behavior and Immunity (2010)

Leonidas Chouliaras Daniël van den Hove Günter Kenis J. Dela Cruz Marijke A.M. Lemmens

Colocalization

Bromodeoxyuridine

10.1016/j.bbi.2010.11.016

Cite

Citations (89)

Epigenetic regulation in the pathophysiology of Alzheimer's disease

Progress in Neurobiology (2010)

Leonidas Chouliaras Bart P. F. Rutten Günter Kenis Odette Peerbooms Pieter Jelle Visser

Epigenesis

Pathophysiology

10.1016/j.pneurobio.2010.01.002

Cite

Citations (252)

Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival

Molecular Psychiatry (2024)

Alexandra T. Strauss Peter G. Swann Stacey L. Kigar Rafailia Christou Natalia Savinykh Yarkoni

Abstract The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g., microglia), peripheral innate immune cells (e.g., blood monocytes, natural killer cells, and dendritic cells) may also differ in these conditions. However, the characterization of peripheral innate immune cell types across different neurodegenerative diseases remains incomplete. This study aimed to characterize peripheral innate immune profiles using flow cytometry for immunophenotyping of peripheral blood mononuclear cells in n = 148 people with Alzheimer’s disease (AD), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), Lewy body dementia (LBD) as compared to n = 37 healthy controls. To compare groups, we used multivariate dissimilarity analysis and principal component analysis across 19 innate immune cell types. We identified pro-inflammatory profiles that significantly differ between patients with all-cause dementia and healthy controls, with some significant differences between patient groups. Regression analysis confirmed that time to death following the blood test correlated with the individuals’ immune profile weighting, positively to TREM2+ and non-classical monocytes and negatively to classical monocytes. Taken together, these results describe transdiagnostic peripheral immune profiles and highlight the link between prognosis and the monocyte cellular subdivision and function (as measured by surface protein expression). The results suggest that blood-derived innate immune profiles can inform sub-populations of cells relevant for specific neurodegenerative diseases that are significantly linked to accelerated disease progression and worse survival outcomes across diagnoses. Blood-based innate immune profiles may contribute to enhanced precision medicine approaches in dementia, helping to identify and monitor therapeutic targets and stratify patients for candidate immunotherapies.

Immunophenotyping

CCL18

Innate lymphoid cell

10.1038/s41380-024-02809-w

Cite

Citations (0)

Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

International Journal of Alzheimer s Disease (2010)

Leonidas Chouliaras Annerieke Sierksma Günter Kenis Jos Prickaerts Marijke A.M. Lemmens

The etiology of the sporadic form of Alzheimer's disease (AD) remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE) may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed.

Apolipoprotein E

Affect

Etiology

10.4061/2010/859101

Cite

Citations (29)

APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure

Brain Communications (2023)

Elijah Mak Maria‐Eleni Dounavi Grégory Operto Elina T Ziukelis P. Simon Jones

The apolipoprotein E ɛ4 allele is the primary genetic risk factor for the sporadic type of Alzheimer's disease. However, the mechanisms by which apolipoprotein E ɛ4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein ɛ4 and its interactions with age and education on cortical microstructure in cognitively normal individuals. Data from 1954 participants were included from the PREVENT-Dementia and ALFA (ALzheimer and FAmilies) studies (mean age = 57, 1197 non-carriers and 757 apolipoprotein E ɛ4 carriers). Structural MRI datasets were processed with FreeSurfer v7.2. The Microstructure Diffusion Toolbox was used to derive Orientation Dispersion Index maps from diffusion MRI datasets. Primary analyses were focused on (i) the main effects of apolipoprotein E ɛ4, and (ii) the interactions of apolipoprotein E ɛ4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E ɛ4 × age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E ɛ4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E ɛ4 carriers with lower years of education. We demonstrated that apolipoprotein E ɛ4 worsened age-related Orientation Dispersion Index decreases in brain regions typically associated with atrophy patterns of Alzheimer's disease. This finding also suggests that apolipoprotein E ɛ4 may hasten the onset age of dementia by accelerating age-dependent reductions in cortical Orientation Dispersion Index.

Apolipoprotein E

10.1093/braincomms/fcad351

Cite

Citations (3)

High dose rivastigmine in the symptom management of Lewy body dementia

BMJ Case Reports (2016)

Joseph Marwan Nour Leonidas Chouliaras Lilian Hickey

A man presented in late 2004 at the age of 65 with a decline in memory. He was diagnosed with Lewy body dementia and started on 3 mg rivastigmine a day, which made a marked clinical improvement. He lived with the illness for 10 years, over which time the dose of acetylcholinesterase inhibitors (ChEI) he took rose to two 9.5 mg rivastigmine patches and 7.5 mg donepezil, significantly above British National Formulary (BNF) limits. He demonstrated clear clinical response to ChEI and showed improvements in alertness and functioning. He did not exhibit life-threatening cardiac side effects and his death in 2014 was not related to the ChEI.

Rivastigmine

Lewy body

Memantine

Cognitive Decline

10.1136/bcr-2016-217240

Cite

Citations (7)

DNA methylation alterations in Lewy Body Dementia

Alzheimer s & Dementia (2023)

Leonidas Chouliaras Alan Thomas Graeme M. Clark Paul C. Donaghy Peter G. Swann

Abstract Background The epigenetic mechanism of DNA methylation has been implicated in the pathophysiology of neurodegenerative disorders such as Lewy body dementia (LBD). DNA methylation profiling may help to identify novel treatment targets and early disease markers. We hypothesized that DNA methylation alterations are detectable in blood due the influence of genetic and environmental factors as well as immune system changes associated with LBD. Method Genome‐wide DNA methylation profiling was carried out using reduced representation bisulfite sequencing in blood samples from 89 LBD patients and 67 controls. Fifty five LBD patients had amyloid PET imaging. Data processing was performed using FastQC, TrimGalore, Bismark and MethylKit. DNA methylation alterations at specific CpG sites as well as at promoter, CpG island and CpG shore regions were compared between LBD cases and controls. A log odds logistic regression was used to identify differential DNA methylation after adjusting for age, sex and smoking status. The false discovery rate (FDR) was used for correction for multiple testing. We also tested the diagnostic classification performance of the differentially methylated regions using receiver operating characteristic (ROC) curve analysis and examined the potential of DNA methylation as a predictor of amyloid PET positivity in LBD. Result Two single CpG sites at TNFRSF1B and EMC6 and three CpG shore regions at ABCG5, ETAA1 and TENM4 reached genome‐wide significance in the differential DNA methylation analysis comparing LBD cases and controls. The combined panel of the top three differentially methylated CpG shores reached an area under the curve (AUC) of 0.91 for the diagnosis of LBD compared to controls (sensitivity 0.89, specificity 0.85). DNA methylation at TENM4 was associated with amyloid PET positivity in LBD with an AUC of 0.84 (sensitivity 0.99, specificity 0.55). Conclusion Our data suggest that DNA methylation alterations in blood are observed in a cohort of LBD patients compared to controls. Our findings need to be replicated in larger cohorts and tested for specificity in LBD in order to explore their future potential as diagnostic markers and/or targets for novel therapeutics.

CpG site

10.1002/alz.078900

Cite

Citations (0)