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Articles by Simon Laws
Comparing pathway-informed polygenic risk score strategies on a multi-cohort evaluation of amyloid-β positivity
Abstract To systematically evaluate pathway-informed polygenic risk score (PRS) strategies and determine which approaches most effectively leverage biological annotations for risk prediction, using brain amyloid-β (Aβ) positivity as a case study. We systematically benchmarked approaches for integrating pathway information into PRSs construction to predict brain Aβ positivity.
Exploring the relationship between methylation of the cortisol receptor genes and brain and cognitive outcomes in individuals with elevated amyloid-β
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Abstract Chronic psychological stress has been implicated as a risk factor for Alzheimer’s disease (AD), potentially through cortisol-mediated acceleration of disease progression. However, the molecular pathways underlying this relationship remain poorly understood. Epigenetic regulation of the glucocorticoid and mineralocorticoid receptor genes (NR3C1 and NR3C2), which encode receptors for cortisol, may play an important role, but has not been examined in relation to AD progression.
By Ayeisha Milligan Armstrong, Lidija Milicic, Michael Vacher, Eleanor K. O’Brien, Vincent Doré, Pierrick Bourgeat, Rosita Shishegar, Ying Xia, Christopher Rowe, Victor L. Villemagne, Paul Maruff, Colin Masters, Giuseppe Verdile, Simon Laws, David Groth, Tenielle Porter, Lifestyle study, Shane Fernandez
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Nature
Verified
Peripheral DNA methylation of candidate Alzheimer’s disease risk genes and its associations with cognition, brain volume and amyloid-β burden
Abstract Alzheimer’s disease (AD) is a growing major public health issue, affecting millions of people worldwide. Genome-wide association studies (GWAS) have identified over 50 loci associated with late-onset AD risk. However, most disease-associated variants are located in noncoding regions of the genome, making it difficult to elucidate exactly how disease risk is affected.
The Florey Institute is publishing many new papers, and this is...
The Florey Institute is publishing many new papers, and this is one of them, targeting patient selection for a new AD intervention study (?). The better we know the risk factors, the better they will find the best outcome measures. Of course, improved cognition is the main goal. ATH434 study in AD is IMO one of the issues that will be negotiated with the big pharma. [Preprint].2026 May 27:2026.05.25.26354071. doi: 10.64898/2026.05.25.26354071.
Calcium supplementation and the risk of dementia in the Perth Longitudinal Study of Aging Women: a post-hoc analysis of a randomised clinical trial for fracture prevention
Keywords Healthy aging Calcium supplementation Cognitive health Dementia Women's health Abbreviations 25OHD (25-Hydroxyvitamin D) AMS (Abbreviated mental test scores) APOE (Apolipoprotein E) ASVD (Atherosclerotic vascular disease) BMI (Body mass index) CAIFOS (Calcium intake fracture outcome study) CI (Confidence interval) CIMT (Carotid intimal medial thickness) CVD (Cardiovascular disease) HR (Hazard ratio) ICD-10-AM (International statistical classification of disease and related health...
Transferability of European-derived Alzheimer’s disease polygenic risk scores across multiancestry populations - Nature Genetics
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Abstract A polygenic score (PGS) for Alzheimer’s disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries.
By Aude Nicolas, Richard Sherva, Yoontae Kim, Masataka Kikuchi, Itziar de Rojas, Maria Carolina Dalmasso, Xiaopu Zhou, Yann Le Guen, Maëlenn Guerchet, Céline Bellenguez, Fahri Küçükali, Claudia L. Satizabal, Bernard Fongang, Qiong Yang, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Steffi G. Riedel-Heller, Lucrezia Hausner, Laura Molina-Porcel, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Oriol Dols-Icardo, Fermín Moreno, Jordi Pérez-Tur, Maria Bullido, Victoria Alvarez, Han Cao, Nancy Y. Ip, Natividad Olivar, Carolina Muchnik, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M. Real, Jose María García-Alberca, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Sami Heikkinen, Jakub Hort, Jesper Qvist Thomassen, Henne Holstege, Harro Seelaar, Philip Scheltens, Maria F. Mahecha, Vera Fominykh, Geir Selbæk, Vilmantas Giedraitis, Anne Boland, Teresa Juárez-Cedillo, Lindsay A Farrer, Ellen M. Wijsman, Richard Mayeux, Margaret A. Pericak-Vance, Alison Goate, Badri Vardarajan, Yuk Yee Leung, Clifton L. Dalgard, Gaël Nicolas, David Wallon, Carole Dufouil, Stéphanie Debette, Edna Grünblatt, Bárbara Angel, Sergio Gloger, Paulina Orellana, Christian González-Billault, Cecilia Albala, Perminder S Sachdev, Karen A. Mather, Richard L Hauger, Victoria Merritt, Roberta Ghidoni, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Benedetta Nacmias, Jenifer S. Yokoyama, Akinori Miyashita, Norikazu Hara, Kouichi Ozaki, Julie Williams, Philippe Amouyel, Andy Saykin, Patrick Kehoe, Cornelia van Duijn, Ruth Frikke-Schmidt, Magda Tsolaki, Tenielle Porter, Simon Laws, Kristel Sleegers, Martin Ingelsson, Sudha Seshadri, Giacomina Rossi, Rebecca Sims, Ole A. Andreassen, Carlos Cruchaga, Valentina Escott-Price, Agustín Ruiz, Kun Ho Lee, Takeshi Ikeuchi, Alfredo M. Ramirez, Alfredo Ramírez, Mark W. Logue
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Nature
Verified
Genomic Characterisation of the Relationship and Causal Links Between Vascular Calcification, Alzheimer’s Disease, and Cognitive Traits
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
Alzheimer’s disease biological PET staging using plasma p217+tau - Communications Medicine
Abstract Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer’s disease (AD) neuropathology. However, their ability to substitute for tau PET to identify AD biological stage is unclear. Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, 18F-NAV4694 Aβ-PET (A) and 18F-MK6240 tau-PET (T) data.
Specific vegetable types are associated with lower long-term risk for late-life dementia: the Perth Longitudinal Study of Aging Women
Specific vegetable types are associated with lower long-term risk for late-life dementia: the Perth Longitudinal Study of Aging Women This study examined the relationship between total vegetable intake, including specific vegetable types with long-term late-life dementia (LLD) risk in older Australian women. 1206 community-dwelling older women aged ≥70 years were included.
CYP1B1-RMDN2 Alzheimer’s disease endophenotype locus identified for cerebral tau PET - Nature Communications
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Abstract Determining the genetic architecture of Alzheimer’s disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition.
By Shannon L. Risacher, Paula J Bice, Jared Brosch, Kelley Faber, Martin R Farlow, Tatiana Foroud, Thea J. Rosewood, Jun kim, Kelly Nudelman, Meichen Yu, Reisa Sperling, William Jagust, Aparna Vasanthakumar, Vincent Doré, Simon Laws, Tenielle Porter, Christopher Rowe, Timothy J. Hohman, Rachel Buckley, Hyun-Sik Yang, Ronald Petersen, Vijay Ramanan, Nilüfer Ertekin-Taner, Prashanthi Vemuri, M. Ilyas Kamboh, Oscar Lopez Verified, Muhammad Shoaib Ali, Carlos Cruchaga, Diana A. Hobbs, Vaishnavi Jadhav, Bruce Lamb, Andy P. Tsai, Isabel Castanho, Jonathan Mill, Lifestyle study
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Nature
Verified
Investigating Genetic Overlap between Alzheimer’s Disease, Lipids, and Coronary Artery Disease: A Large-Scale Genome-Wide Cross Trait Analysis
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
Newly launched local mental health investment fund | News centre-Guildford and Waverley Alliance
The Children and Young People’s Mental Health Investment Fund (MHIF) is a resource to enable the delivery of community-based, prevention and early mental health support for children and young people.
Pop up Covid-19 booster clinics available across Surrey | News centre
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Geotools - cropping a coverage doesn't remove rings/holes. Is there a way?
Cropping a geotools coverage using a polygon geometry works well, for example, WKTReader wktReader = new WKTReader(); Geometry polygon = wktReader.read("Polygon ((-44.84843762765495967 23.50485000755512388, -44.52609517919035653 24.23955870035893767, -43.1982367347690186 24.78673572524395396, -41.84151180242547952 23.49161367821367818, -44.84843762765495967 23.50485000755512388))"); ParameterValueGroup params = processor.getOperation("CoverageCrop").getParameters();...
Take time out to check your blood pressure | News centre
It is estimated that 125,900 people in Surrey Heartlands are living with poorly controlled or undiagnosed hypertension. High blood pressure is called ‘the silent killer’ as it has no symptoms, but can lead to heart attacks, stroke and other illnesses. Make sure you get your blood pressure checked so that you can get support to bring your blood pressure down to a healthy level through lifestyle changes or through taking medication.
Weybetter Weybridge: have your say at our latest drop-in event | News centre-North West Surrey Alliance
Weybetter Weybridge: have your say at our latest drop-in event Following previous events that have been held in relation to the new healthcare facility and library developments, we now have final proposed designs that we would like to share with you. The event will be the opportunity see these designs ahead of the submission of the two planning applications in the coming weeks.
Critical incident declared across health services in Surrey Heartlands | News centre
Due to the significant ongoing pressure on local NHS services, alongside the need to act swiftly to ensure patients continue to receive safe, high quality care we have declared a critical incident across health services in Surrey Heartlands.
IJMS | Free Full-Text | Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis
3. Discussion Support for the involvement of the gut–brain link in the risk of AD continues to gather momentum [1,2,3,4,5,6,7]. However, emerging evidence on the connection between cognition and GIT traits is inconsistent [20,21,22,23,31,32]. To advance our understanding on the relationship of cognitive traits and AD with GIT disorders, the present study analysed several large-scale GWAS’ summary data using well-regarded statistical genetic methods.
Current Insights on the Use of Insulin and the Potential Use of Insulin Mimetics in Targeting Insulin Signalling in Alzheimer’s Disease
Abstract : Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology.
Cold weather alert - December 2022 | News centre
Cold weather alert - December 2022 Freezing temperatures are forecast across Surrey this week, with the Met Office issuing an amber Level 3 Cold Weather alert. The warning is in place from 6pm on Wednesday (December 7) and will last until the start of next week. Cold weather can have serious consequences for health, and older people and those with heart or lung conditions can be particularly at risk. Keep yourself safe, warm and look out for others.
WeyBetter Weybridge: health campus pop-up display - save the date. | News centre-North West Surrey Alliance
Local residents are invited to a pop-up display and drop-in session to find out the latest on the redevelopment of healthcare and community facilities in Weybridge. As we reach the next stage of finalising our design for the health campus we want to share the latest concepts with the local community and hear your views. This is also a chance to get an update on renewing the library and plans to improve local roads.
A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders - Communications Biology
Abstract Consistent with the concept of the gut-brain phenomenon, observational studies suggest a relationship between Alzheimer’s disease (AD) and gastrointestinal tract (GIT) disorders; however, their underlying mechanisms remain unclear. Here, we analyse several genome-wide association studies (GWAS) summary statistics (N = 34,652–456,327), to assess the relationship of AD with GIT disorders.
Pharmacies - ICS
As qualified healthcare professionals, Pharmacists can offer clinical advice and over-the-counter medicines for a range of minor illnesses, such as coughs, colds, sore throats, tummy trouble, earache, cystitis, skin rashes, baby teething, red eye and aches and pains. They are also trained to provide health and wellbeing advice.
Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders
Marta F. Nabais1,2, Simon M. Laws3, Tian Lin1, Costanza L. Vallerga1,4, Nicola J. Armstrong5, Ian P. Blair6, John B. Kwok7, Karen A. Mather8,9, George D. Mellick10, Perminder S. Sachdev8,11, Leanne Wallace1, Anjali K. Henders1, 12, Paul J.
Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease
Abstract Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation.
Genetic resilience to Alzheimer's disease in APOE ε4 homozygotes: A systematic review
To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Abstract Introduction Individuals with homozygosity for the apolipoprotein E (APOE) ε4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some individuals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These “resilient” individuals may carry protective genetic factors.
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