Patrick G Kehoe

Summary

Affiliation: University of Bristol
Country: UK

Publications

  1. doi request reprint Current status of renin-aldosterone angiotensin system-targeting anti-hypertensive drugs as therapeutic options for Alzheimer's disease
    Emma Louise Ashby
    University of Bristol, Frenchay Hospital, School of Clinical Sciences, John James Laboratories, Dementia Research Group, Bristol, BS16 1LE, UK
    Expert Opin Investig Drugs 22:1229-42. 2013
  2. doi request reprint Associations of angiotensin targeting antihypertensive drugs with mortality and hospitalization in primary care patients with dementia
    Patrick Gavin Kehoe
    Faculty of Medicine and Dentistry, School of Clinical Sciences, Dementia Research Group, University of Bristol, John James Laboratories, Frenchay Hospital, Bristol, UK
    J Alzheimers Dis 33:999-1008. 2013
  3. doi request reprint The renin-angiotensin system and antihypertensive drugs in Alzheimer's disease: current standing of the angiotensin hypothesis?
    Patrick G Kehoe
    Dementia Research Group, John James Laboratories, Frenchay Hospital, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK
    J Alzheimers Dis 30:S251-68. 2012
  4. pmc Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease
    Onofre Combarros
    Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital University of Cantabria, 39008 Santander, Spain
    J Neuroinflammation 6:22. 2009
  5. pmc The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project
    Onofre Combarros
    Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital University of Cantabria, 39008 Santander, Spain
    BMC Med Genet 11:162. 2010
  6. ncbi request reprint Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?
    Patrick G Kehoe
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol
    Lancet Neurol 6:373-8. 2007
  7. doi request reprint Angiotensins in Alzheimer's disease - friend or foe?
    Patrick G Kehoe
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK
    Trends Neurosci 32:619-28. 2009
  8. ncbi request reprint The renin-angiotensin-aldosterone system and Alzheimer s disease?
    Patrick G Kehoe
    Department of Care of the Elderly, University of Bristol, Bristol, BS16 1LE, UK
    J Renin Angiotensin Aldosterone Syst 4:80-93. 2003
  9. ncbi request reprint TNFR-associated factor-2 (TRAF-2) in Alzheimer's disease
    Doris Culpan
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, John James Buildings, Frenchay Hospital, Bristol, United Kingdom
    Neurobiol Aging 30:1052-60. 2009
  10. ncbi request reprint Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease
    Patrick G Kehoe
    Department of Care of the Elderly, The John James Building, Frenchay Hospital, University of Bristol, UK
    Hum Genet 114:478-83. 2004

Collaborators

Detail Information

Publications48

  1. doi request reprint Current status of renin-aldosterone angiotensin system-targeting anti-hypertensive drugs as therapeutic options for Alzheimer's disease
    Emma Louise Ashby
    University of Bristol, Frenchay Hospital, School of Clinical Sciences, John James Laboratories, Dementia Research Group, Bristol, BS16 1LE, UK
    Expert Opin Investig Drugs 22:1229-42. 2013
    ..All of these are generally well tolerated and have been shown to offer varying degrees of protection on aspects of cognition and dementia, thus making them an attractive therapeutic option for AD...
  2. doi request reprint Associations of angiotensin targeting antihypertensive drugs with mortality and hospitalization in primary care patients with dementia
    Patrick Gavin Kehoe
    Faculty of Medicine and Dentistry, School of Clinical Sciences, Dementia Research Group, University of Bristol, John James Laboratories, Frenchay Hospital, Bristol, UK
    J Alzheimers Dis 33:999-1008. 2013
    ..Further evidence is required to either support or refute the observation that exposure to angiotensin converting enzyme inhibitors in patients with dementia is associated with increased mortality...
  3. doi request reprint The renin-angiotensin system and antihypertensive drugs in Alzheimer's disease: current standing of the angiotensin hypothesis?
    Patrick G Kehoe
    Dementia Research Group, John James Laboratories, Frenchay Hospital, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK
    J Alzheimers Dis 30:S251-68. 2012
    ....
  4. pmc Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease
    Onofre Combarros
    Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital University of Cantabria, 39008 Santander, Spain
    J Neuroinflammation 6:22. 2009
    ....
  5. pmc The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project
    Onofre Combarros
    Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital University of Cantabria, 39008 Santander, Spain
    BMC Med Genet 11:162. 2010
    ..We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls...
  6. ncbi request reprint Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?
    Patrick G Kehoe
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol
    Lancet Neurol 6:373-8. 2007
    ....
  7. doi request reprint Angiotensins in Alzheimer's disease - friend or foe?
    Patrick G Kehoe
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK
    Trends Neurosci 32:619-28. 2009
    ..This paper reviews molecular, genetic, experimental and clinical data as well as the therapeutic opportunities that relate to the involvement of the RAS in AD...
  8. ncbi request reprint The renin-angiotensin-aldosterone system and Alzheimer s disease?
    Patrick G Kehoe
    Department of Care of the Elderly, University of Bristol, Bristol, BS16 1LE, UK
    J Renin Angiotensin Aldosterone Syst 4:80-93. 2003
    ....
  9. ncbi request reprint TNFR-associated factor-2 (TRAF-2) in Alzheimer's disease
    Doris Culpan
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, John James Buildings, Frenchay Hospital, Bristol, United Kingdom
    Neurobiol Aging 30:1052-60. 2009
    ..The 3' UTR SNP (rs7852970) GG allele was significantly protective against AD (p=0.030). Our findings suggest that the TRAF-2 pathway is involved AD. The mechanisms are currently unclear and need further examination...
  10. ncbi request reprint Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease
    Patrick G Kehoe
    Department of Care of the Elderly, The John James Building, Frenchay Hospital, University of Bristol, UK
    Hum Genet 114:478-83. 2004
    ..These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology...
  11. doi request reprint Oxidative balance in Alzheimer's disease: relationship to APOE, Braak tangle stage, and the concentrations of soluble and insoluble amyloid-β
    Hannah Tayler
    Dementia Research Group, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK
    J Alzheimers Dis 22:1363-73. 2010
    ..Increased β-secretase activity associated with oxidative stress is likely to contribute to the accumulation of Aβ and this, in turn, to induce antioxidant capacity...
  12. ncbi request reprint APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease
    Katy A Chalmers
    University of Bristol, Department of Care of the Elderly, Frenchay Hospital, Bristol BS16 1LE, UK
    Neuroreport 15:95-8. 2004
    ..Here we report that polymorphisms within the APOE promoter, ACE1 and CYP46 gene are not risk factors for AD and are not associated with parenchymal or vascular accumulation of Abeta...
  13. doi request reprint Higher soluble amyloid beta concentration in frontal cortex of young adults than in normal elderly or Alzheimer's disease
    Zoë van Helmond
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, UK
    Brain Pathol 20:787-93. 2010
    ....
  14. doi request reprint Endothelin-1 is elevated in Alzheimer's disease and upregulated by amyloid-β
    Jennifer C Palmer
    Dementia ResearchGroup, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK
    J Alzheimers Dis 29:853-61. 2012
    ..024). These findings provide evidence of overactivity of the endothelin system in AD, further supporting the suggestion that endothelin receptor antagonists may be of value for the treatment of this disease...
  15. pmc Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia
    Rachel Barker
    1 Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK
    Brain 137:1524-32. 2014
    ....
  16. doi request reprint Influence of LRP-1 and apolipoprotein E on amyloid-β uptake and toxicity to cerebrovascular smooth muscle cells
    Wan Adriyani W Ruzali
    Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK
    J Alzheimers Dis 33:95-110. 2013
    ..This may contribute to the differential effects of APOE genotype on severity of CAA and the risk of rupture of Aβ-laden blood vessels...
  17. doi request reprint Assessment of activation of the plasma kallikrein-kinin system in frontal and temporal cortex in Alzheimer's disease and vascular dementia
    Emma L Ashby
    Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK
    Neurobiol Aging 33:1345-55. 2012
    ..PK activity was significantly increased in the frontal and temporal cortex in AD. Increased PK activity in AD is likely to contribute to increased BK release and may thereby influence cerebral blood flow and vascular permeability...
  18. doi request reprint Associations of anti-hypertensive treatments with Alzheimer's disease, vascular dementia, and other dementias
    Neil M Davies
    School of Social and Community Medicine, Faculty of Medicine and Dentistry, University of Bristol, Canynge Hall, Bristol, UK
    J Alzheimers Dis 26:699-708. 2011
    ..Patients with AD were around half as likely to be prescribed ARBs. Further randomized controlled trial evidence is required to rigorously test these findings...
  19. ncbi request reprint LRP1 expression in cerebral cortex, choroid plexus and meningeal blood vessels: relationship to cerebral amyloid angiopathy and APOE status
    Wan Adriyani W Ruzali
    Dementia Research Group, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, BS16 1LE, UK
    Neurosci Lett 525:123-8. 2012
    ..These findings suggest that APOE may influence the severity of CAA through altered expression of LRP1...
  20. doi request reprint Clusterin mRNA and protein in Alzheimer's disease
    Shabnam Baig
    Dementia Research Group, Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, UK
    J Alzheimers Dis 28:337-44. 2012
    ..The increase in clusterin noted in peripheral blood in AD may reflect increased passage of this chaperone protein across the blood-brain barrier but further work is needed to determine how CLU variants influence the development of AD...
  21. doi request reprint Changes with age in the activities of beta-secretase and the Abeta-degrading enzymes neprilysin, insulin-degrading enzyme and angiotensin-converting enzyme
    J Scott Miners
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, Bristol, UK
    Brain Pathol 20:794-802. 2010
    ..Further research is needed to establish whether these changes in enzyme activity and Abeta levels are causally related and if so how...
  22. doi request reprint Oligomeric Abeta in Alzheimer's disease: relationship to plaque and tangle pathology, APOE genotype and cerebral amyloid angiopathy
    Zoë van Helmond
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, Bristol, UK
    Brain Pathol 20:468-80. 2010
    ....
  23. ncbi request reprint Protein and gene expression of tumour necrosis factor receptors I and II and their promoter gene polymorphisms in Alzheimer's disease
    Doris Culpan
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol, United Kingdom
    Exp Gerontol 42:538-44. 2007
    ..Our findings suggest that TNF-RI and -RII promoter gene polymorphisms and variations in protein and gene expression of these receptors are unlikely to play a major role in the development of AD...
  24. ncbi request reprint Neither sequence variation in the IL-10 gene promoter nor presence of IL-10 protein in the cerebral cortex is associated with Alzheimer's disease
    Doris Culpan
    Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, John James Buildings, Frenchay Hospital, Frenchay, Bristol, BS16 1LE, United Kingdom
    Neurosci Lett 408:141-5. 2006
    ..Levels of IL-10 protein and gene expression examined also did not appear to be related to AD. Despite this being a relatively small sample, these data suggest that IL-10 does not play a major role in the development of AD...
  25. ncbi request reprint Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease
    Doris Culpan
    Department of Care of the Elderly, University of Bristol, John James Buildings, Frenchay Hospital, Frenchay, Bristol, BS16 1LE, UK
    Neurosci Lett 350:61-5. 2003
    ..014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD...
  26. doi request reprint Activators and inhibitors of the plasminogen system in Alzheimer's disease
    Rachel Barker
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Sciences at North Bristol, Bristol University, Bristol, UK
    J Cell Mol Med 16:865-76. 2012
    ..The increases in tPA, uPA, PAI-1 and α2-antiplasmin may counteract each other so that plasmin activity is not significantly altered in AD, but increased tPA may also affect synaptic plasticity, excitotoxic neuronal death and apoptosis...
  27. pmc Endothelin-converting enzyme-2 is increased in Alzheimer's disease and up-regulated by Abeta
    Jennifer C Palmer
    Dementia Research Group, Frenchay Hospital, Bristol, United Kingdom
    Am J Pathol 175:262-70. 2009
    ..Our findings suggest that endothelin-1 receptor antagonists, already licensed for treating other diseases, could be of benefit in AD therapies...
  28. pmc Distribution and expression of picalm in Alzheimer disease
    Shabnam Baig
    Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, United Kingdom
    J Neuropathol Exp Neurol 69:1071-7. 2010
    ..Further research is needed to determine whether PICALM expression is influenced by Aβ levels and whether it affects Aβ uptake and transport by endothelial cells...
  29. doi request reprint Kallikrein-related peptidase 6 in Alzheimer's disease and vascular dementia
    Emma L Ashby
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, UK
    Brain Res 1363:1-10. 2010
    ..In VaD, KLK6 protein level was significantly increased in the frontal cortex. Our findings suggest that an altered KLK6 expression may contribute to vascular abnormalities in AD and VaD...
  30. pmc The influence of tumour necrosis factor- α (TNF-α) on amyloid-β (Aβ)-degrading enzymes in vitro
    Doris Culpan
    Dementia Research Group, School of Clinical Sciences, University of Bristol, John James Building, Frenchay Hospital Bristol, BS16 1LE, United Kingdom
    Int J Mol Epidemiol Genet 2:409-15. 2011
    ..In conclusion, apart from a transient reduction in ECE-2 protein levels, TNF-α had no impact in our in vitro experimental system on transcription or translation of any of our selected mediators of Aβ degradation...
  31. pmc CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer's disease
    Heather J M Weir
    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    PLoS ONE 7:e48225. 2012
    ..Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress...
  32. doi request reprint Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation
    Jonathon Hull
    Faculty of Health and Life Sciences, University of the West of England, Bristol, UK
    J Neurochem 123:997-1009. 2012
    ....
  33. doi request reprint Plasminogen and plasmin in Alzheimer's disease
    Rachel Barker
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Sciences at North Bristol, Bristol University, Bristol, UK
    Brain Res 1355:7-15. 2010
    ..Plasmin activity was reduced in AD but this did not reach statistical significance. In contrast to some studies these data do not support the involvement of plasmin in the abnormal accumulation of Aβ in AD...
  34. doi request reprint Abeta-degrading enzymes in Alzheimer's disease
    James Scott Miners
    Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK
    Brain Pathol 18:240-52. 2008
    ....
  35. pmc Genetic variation in MME in relation to neprilysin protein and enzyme activity, Aβ levels, and Alzheimer's disease risk
    Scott Miners
    Dementia Research Group, University of Bristol, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK
    Int J Mol Epidemiol Genet 3:30-8. 2012
    ..055). These data suggest that MME variation may be associated with AD risk but we have not found evidence that this is mediated through modification of NEP protein level or activity...
  36. pmc Tumour necrosis factor-α (TNF-α) and miRNA expression in frontal and temporal neocortex in Alzheimer's disease and the effect of TNF-α on miRNA expression in vitro
    Doris Culpan
    Dementia Research Group, School of Clinical Sciences, University of Bristol, John James Buildings, Frenchay Hospital Frenchay, Bristol, BS16 1LE, United Kingdom
    Int J Mol Epidemiol Genet 2:156-62. 2011
    ..Our brain tissue findings argue against a role for TNF-α in influencing the expression of these miRNAs in AD...
  37. doi request reprint Calcium channel blockers and Alzheimer's disease: potential relevance in treatment strategies of metabolic syndrome
    William V Goodison
    Dementia Research Group, John James Laboratories, Frenchay Hospital, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK
    J Alzheimers Dis 30:S269-82. 2012
    ..We explore the possibility of whether CCBs acting in the brain may delay the onset and progression of AD and thus may inform treatment regimes in people with MetS...
  38. ncbi request reprint Haplotypes extending across ACE are associated with Alzheimer's disease
    Patrick G Kehoe
    Department of Care of the Elderly, University of Bristol, The John James Building, Frenchay Hospital, Bristol, UK
    Hum Mol Genet 12:859-67. 2003
    ..Results support a model whereby decreased ACE activity may influence AD susceptibility by a mechanism involving beta-amyloid metabolism...
  39. ncbi request reprint Genetic variants of ABCA1 modify Alzheimer disease risk and quantitative traits related to beta-amyloid metabolism
    Hagit Katzov
    Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden
    Hum Mutat 23:358-67. 2004
    ..Results indicate that variants of ABCA1 may affect the risk of AD, providing further support for a genetic link between AD and cholesterol metabolism...
  40. ncbi request reprint Differences in allele frequencies of ACE I/D polymorphism between Northern and Southern Europe at different ages
    Francesco Panza
    Atherosclerosis 193:455-7. 2007
  41. ncbi request reprint Sequence variants of IDE are associated with the extent of beta-amyloid deposition in the Alzheimer's disease brain
    Mia E L Blomqvist
    Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden
    Neurobiol Aging 26:795-802. 2005
    ..Results indicate that alleles of IDE contribute to variability in A beta deposition in the AD brain and suggest that this relationship may have relevance for the degree of cognitive dysfunction in AD patients...
  42. ncbi request reprint Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease
    Donald J Lehmann
    The Oxford Project to Investigate Memory and Ageing OPTIMA, Department of Pharmacology, University of Oxford, Oxford, United Kingdom
    Am J Epidemiol 162:305-17. 2005
    ..This interaction warrants further investigation...
  43. ncbi request reprint Current knowledge of chromosome 12 susceptibility genes for late-onset Alzheimer's disease
    Alessia D'Introno
    Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Policlinico, Piazza Giulio Cesare, 11 70124 Bari, Italy
    Neurobiol Aging 27:1537-53. 2006
    ..This paper reviews studies that have provided evidence of linkage for AD on chromosome 12 and in turn discusses the work conducted to date on candidate genes that have been identified and map to the chromosome 12 regions of interest...
  44. doi request reprint Clearance of Abeta from the brain in Alzheimer's disease. Foreword
    Seth Love
    Brain Pathol 18:239. 2008
  45. pmc Evidence that the gene encoding insulin degrading enzyme influences human lifespan
    Mun Gwan Hong
    Department of Medical Epidemiology and Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Hum Mol Genet 17:2370-8. 2008
    ....
  46. ncbi request reprint Angiotensin I converting enzyme (ACE) gene polymorphism in centenarians: different allele frequencies between the North and South of Europe
    Francesco Panza
    Department of Geriatrics, Centre for Aging Brain, Memory Unit, University of Bari, Policlinico, Piazza Giulio Cesare, 11, Bari 70124, Italy
    Exp Gerontol 38:1015-20. 2003
    ..Such genetic differences in conjunction with differing environmental factors may explain in part previous results suggesting a role of this polymorphism in longevity...
  47. ncbi request reprint Sex differences in the association of apolipoprotein E and angiotensin-converting enzyme gene polymorphisms with healthy aging and longevity: a population-based study from Southern Italy
    Davide Seripa
    Laboratory of Geriatrics and Gerontology, Research Department, IRCCS Casa Sollievo della Sofferenza, Viale San Giovanni Rotondo, Italy
    J Gerontol A Biol Sci Med Sci 61:918-23. 2006
    ..636). Heterosis was also observed at the ACE locus. No relationship between apoE and ACE polymorphism was found. These findings suggest a role of sex in the association of apoE and ACE gene polymorphisms with healthy aging and longevity...