Patrick G. Kehoe
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View article: Androgen Effects on Amyloid Precursor Protein Processing Pathways in Cancer: A Systematic Review
Androgen Effects on Amyloid Precursor Protein Processing Pathways in Cancer: A Systematic Review Open
Androgens have been shown to be linked to cancer progression, particularly in hormone-dependent cancers such as prostate and breast cancer, but also other cancers. Amyloid precursor protein (APP), which has primarily been studied in Alzhei…
View article: Blood markers of the renin‐angiotensin system and cognitive impairment: The Look AHEAD Study
Blood markers of the renin‐angiotensin system and cognitive impairment: The Look AHEAD Study Open
Background The renin‐angiotensin system (RAS) has been proposed as a potential modifier of the development of Alzheimer's disease (AD). However, prospective studies are sparse. We aimed to determine whether plasma ACE‐1, ACE‐2, angiotensin…
View article: GIGAVCID: A Genome‐Wide Meta‐Analysis of 1.1 Million Individuals Identifies Novel Genetic Loci for Vascular Cognitive Impairment
GIGAVCID: A Genome‐Wide Meta‐Analysis of 1.1 Million Individuals Identifies Novel Genetic Loci for Vascular Cognitive Impairment Open
Background Vascular cognitive impairment and dementia (VCID) is a leading cause of cognitive decline and often coexists with neurodegenerative pathologies such as Alzheimer's disease (AD). Despite its clinical significance, the genetic arc…
View article: Elevated Na <sup>+</sup> /K <sup>+</sup> Ratio in Alzheimer’s Disease: A Potential Biomarker for Braak Stage
Elevated Na <sup>+</sup> /K <sup>+</sup> Ratio in Alzheimer’s Disease: A Potential Biomarker for Braak Stage Open
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and the accumulation of amyloid plaques and neurofibrillary tangles. While prior research has focused mainly on protein aggr…
View article: Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer’s Disease in European Populations: Development and Validation
Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer’s Disease in European Populations: Development and Validation Open
Objectives Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer’s disease (AD). In this study, we present an improved PHS model for AD that incorporates a large number…
View article: Machine learning in Alzheimer’s disease genetics
Machine learning in Alzheimer’s disease genetics Open
Traditional statistical approaches have advanced our understanding of the genetics of complex diseases, yet are limited to linear additive models. Here we applied machine learning (ML) to genome-wide data from 41,686 individuals in the lar…
View article: Does blood pressure level matter more in individuals with higher genetic risk of dementia? A polygenic interaction study in the UK Biobank
Does blood pressure level matter more in individuals with higher genetic risk of dementia? A polygenic interaction study in the UK Biobank Open
Background & Aims The causal role of blood pressure (BP) in dementia remains debated. BP may act as an effect modifier; whereby elevated pressure accelerates cognitive decline in the presence of existing neurodegenerative or cerebrovascula…
View article: Causes and consequences of vascular dementia across the life course: Evidence from a UK Biobank phenome-wide and Mendelian randomization study
Causes and consequences of vascular dementia across the life course: Evidence from a UK Biobank phenome-wide and Mendelian randomization study Open
Background Vascular dementia (VaD) is the second most common cause of dementia, yet its risk factors and biological mechanisms remain poorly understood. Objective To identify causes and consequences of VaD by developing a polygenic risk sc…
View article: Dissecting the effect of long-term exposure to air pollution on risk of dementia in UK Biobank
Dissecting the effect of long-term exposure to air pollution on risk of dementia in UK Biobank Open
Mounting evidence links air pollution to dementia, the most prevalent cause of cognitive impairment in older people. Here we investigated individual and compound effects of particulate matters (PM 10 , PM 2.5 , PM coarse , PM abs ) and nit…
View article: Repurposing drugs for the prevention of vascular dementia: Evidence from drug target Mendelian randomization
Repurposing drugs for the prevention of vascular dementia: Evidence from drug target Mendelian randomization Open
Importance Vascular dementia (VaD) is a devastating cerebrovascular disease with no disease-modifying treatments available. Repurposing existing drugs for VaD risk factors could have an important clinical impact. Objective To determine whe…
View article: Curious Dichotomies of Apolipoprotein E Function in Alzheimer’s Disease and Cancer—One Explanatory Mechanism of Inverse Disease Associations?
Curious Dichotomies of Apolipoprotein E Function in Alzheimer’s Disease and Cancer—One Explanatory Mechanism of Inverse Disease Associations? Open
An apparent “inverse” relationship exists between two seemingly unconnected conditions, Alzheimer’s disease (AD) and cancer, despite sharing similar risk factors, like increased age and obesity. AD is associated with amyloid beta (Aβ) plaq…
View article: Curious Dichotomies of Apolipoprotein E Function in Alzheimer’s Disease and Cancer—One Explanatory Mechanism of Inverse Disease Associations?
Curious Dichotomies of Apolipoprotein E Function in Alzheimer’s Disease and Cancer—One Explanatory Mechanism of Inverse Disease Associations? Open
An apparent "inverse" relationship exists between two seemingly unconnected conditions: Alzheimer's disease (AD) and cancer, despite sharing similar risk factors, like increased age and obesity. AD is associated with amyloid beta (Aβ)…
View article: Association between plasma angiotensin converting enzyme 1 level and cognition over 12‐years: The Look AHEAD Study
Association between plasma angiotensin converting enzyme 1 level and cognition over 12‐years: The Look AHEAD Study Open
Background The renin angiotensin system (RAS) has been proposed as a potential modifier of the development of Alzheimer’s disease (AD). However, prospective studies of RAS are sparse especially among cognitively normal individuals with typ…
View article: Decentralised clinical trials for medications to reduce the risk of dementia: consensus report and guidance
Decentralised clinical trials for medications to reduce the risk of dementia: consensus report and guidance Open
Background Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralised clinical trials in dementia. There are many potential benefits associated with decentralise…
View article: Extremely rare CNVs contributing to Alzheimer disease risk: a case-control association analysis of exome sequencing data from 22,319 individuals
Extremely rare CNVs contributing to Alzheimer disease risk: a case-control association analysis of exome sequencing data from 22,319 individuals Open
Rare coding single nucleotide variants (SNV) and short insertions or deletions (indels) contribute to Alzheimer disease (AD) genetic risk, from pathogenic variants in autosomal dominant genes to risk factors with diverse effects. In contra…
View article: Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease
Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease Open
Tubulin associated unit has been extensively studied in neurodegenerative diseases including Alzheimer's disease (AD), whereby its hyperphosphorylation and accumulation contributes to disease pathogenesis. Tau is abundantly expressed in th…
View article: Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance
Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance Open
INTRODUCTION Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentrali…
View article: X-Chromosome-wide association study for Alzheimer’s disease
X-Chromosome-wide association study for Alzheimer’s disease Open
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To finally address this and better characterize the genetic landscape of AD, we performed an in…
View article: Dysregulation of the renin‐angiotensin system in vascular dementia
Dysregulation of the renin‐angiotensin system in vascular dementia Open
The renin‐angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS …
View article: Angiotensin-converting enzyme 2 (ACE-2) is dysregulated in Alzheimer's disease but not Vascular dementia
Angiotensin-converting enzyme 2 (ACE-2) is dysregulated in Alzheimer's disease but not Vascular dementia Open
Introduction: The brain renin-angiotensin system (RAS) is dysregulated in dementia. We have previously shown that ACE-2, a central regulator of the protective counter-regulatory arm of RAS, is inversely associated with disease pathology in…
View article: Angiotensin‐converting enzyme‐1, ACE‐1, and ACE‐2 are dysregulated in Alzheimer’s disease and related to ACE1 genotype
Angiotensin‐converting enzyme‐1, ACE‐1, and ACE‐2 are dysregulated in Alzheimer’s disease and related to ACE1 genotype Open
Background The renin‐angiotensin system (RAS) is dysregulated in Alzheimer’s disease (AD): angiotensin‐converting enzyme (ACE‐1) activity, a rate‐limiting enzyme in the disease‐associated classical RAS (cRAS) pathway, is elevated, whereas …
View article: sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study
sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study Open
INTRODUCTION There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high‐risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (C…
View article: Altered Gene Expression Within the Renin–Angiotensin System in Normal Aging and Dementia
Altered Gene Expression Within the Renin–Angiotensin System in Normal Aging and Dementia Open
The renin–angiotensin system (RAS) is dysregulated in Alzheimer’s disease (AD). In this study, we have explored the hypothesis that an age-related imbalance in brain RAS is a trigger for RAS dysregulation in AD. We characterized RAS gene…