Research Topics
Species | S G YounkinSummaryAffiliation: Mayo Clinic Country: USA Publications
Research Grants
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Publications
Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control studyMinerva M Carrasquillo
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Mol Neurodegener 6:54. 2011..abstract:..- Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implicationsMariet Allen
Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL, USA
Mol Neurodegener 7:13. 2012..4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects)... - Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease riskChristopher R Simmons
Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Mol Neurodegener 6:62. 2011..abstract:.. - Rheumatoid arthritis-associated polymorphisms are not protective against Alzheimer's diseaseChristopher R Simmons
Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Mol Neurodegener 6:33. 2011..abstract:.. - Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brainKarrie E Grear
Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Mol Neurodegener 4:46. 2009..abstract:.. - Investigation of 15 of the top candidate genes for late-onset Alzheimer's diseaseOlivia Belbin
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Hum Genet 129:273-82. 2011..Overall, this large, independent follow-up study for 15 of the top LOAD candidate genes provides support for GAB2 and LOC651924 (6q24.1) as risk modifiers of LOAD and novel associations between PGBD1 and EBF3 with age-at-onset... 
Amyloid beta vaccination: reduced plaques and improved cognitionS G Younkin
Center for Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
Nat Med 7:18-9. 2001..Immunization with an amyloid beta-peptide fragment reduces learning and memory impairments in mice, and this approach may eventually be used to prevent and/or treat this disease in people...- Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigreesN Ertekin-Taner
Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA
Science 290:2303-4. 2000..Remarkably, linkage to the same region was obtained independently in a genome-wide screen of LOAD sibling pairs. These results provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase Abeta... - Reduction of Abeta accumulation in the Tg2576 animal model of Alzheimer's disease after oral administration of the phosphatidyl-inositol kinase inhibitor wortmanninS J Haugabook
Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
FASEB J 15:16-18. 2001.... - Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's diseaseT E Golde
Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA
Biochim Biophys Acta 1502:172-87. 2000..This review will highlight those aspects of Abeta biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study... - Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's diseaseT Kawarabayashi
Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
J Neurosci 21:372-81. 2001..If a similar decline occurs in human plasma, it is possible that measurement of plasma Abeta may be useful as a premorbid biomarker for AD... - Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid depositionP Das
Department of Neurosciences, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Neurobiol Aging 22:721-7. 2001..These results indicate that in Tg2576 mice, Abeta1-42 immunization is more effective at preventing additional Abeta accumulation and does not result in significant clearance of pre-existing Abeta deposits... - Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigreesN Ertekin-Taner
Mayo Clinic Jacksonville, Jacksonville, Florida, 32224, USA
Genet Epidemiol 21:19-30. 2001..Thus, we suggest that plasma Abeta levels are quantitative traits that may be excellent surrogate markers for use in linkage analysis to identify loci that are important in typical LOAD... - Glycosylphosphatidylinositol-anchored proteins play an important role in the biogenesis of the Alzheimer's amyloid beta-proteinK Sambamurti
Mayo Clinic, Jacksonville, Florida 32224, USA
J Biol Chem 274:26810-4. 1999..The cell-surface GPI-anchored protein(s) involved in Abeta biogenesis may be excellent therapeutic target(s) in Alzheimer's disease... - Amyloid beta protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brainY Harigaya
Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Biochem Biophys Res Commun 276:422-7. 2000..In vitro comparison of Abeta1-42 and Abeta3(pE)-42 showed that Abeta3(pE)-42 is highly prone to oligomerization. These findings suggest that Abeta3(pE)-42 may be particularly important in AD pathogenesis... - High throughput screens for the identification of compounds that alter the accumulation of the Alzheimer's amyloid beta peptide (Abeta)S J Haugabook
Mayo Clinic Jacksonville, Birdsall Building Room 253, 4500 San Pablo Road, Jacksonville, FL 32224, USA
J Neurosci Methods 108:171-9. 2001..If compounds such as these can be identified that lower Abeta in the brain, they may represent one of the fastest and most cost effective methods to therapy... - Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer diseaseNeill R Graff-Radford
Department of Neuroscience, Mayo College of Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
Arch Neurol 64:354-62. 2007..To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease... - TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriersN Finch
Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Neurology 76:467-74. 2011.... - Presenilins as therapeutic targets for the treatment of Alzheimer's diseaseT E Golde
Mayo Clinic Jacksonville, Dept of Neuroscience, 4500 San Pablo Road, 32224, Jacksonville, FL, USA
Trends Mol Med 7:264-9. 2001.... - Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological agingDeng-Shun Wang
Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
J Neuropathol Exp Neurol 64:378-85. 2005..The results add further evidence that PA is distinct from AD and indicate that decreased Abeta degradation by NEP is unlikely to contribute significantly to amyloid deposition in PA or, in many cases, of AD... - Plasma amyloid beta protein is elevated in late-onset Alzheimer disease familiesN Ertekin-Taner
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA
Neurology 70:596-606. 2008..Plasma A beta levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD)... - Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer diseaseNilufer Ertekin-Taner
Mayo Clinic Jacksonville, Department of Neuroscience, Jacksonville, FL, USA
Hum Mutat 23:334-42. 2004..007) in our family series. These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD... - Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator geneNilufer Ertekin-Taner
Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Hum Mol Genet 14:447-60. 2005..PLAU_1 is a plausible pathogenic mutation that could act by increasing Abeta42, but additional biological experiments are required to show this definitively... - A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43)C B Eckman
Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Hum Mol Genet 6:2087-9. 1997.... - Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family membersNiCole Finch
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Brain 132:583-91. 2009..We propose that plasma GRN levels could be used as a reliable and inexpensive tool to identify all GRN mutation carriers in early-onset dementia populations and asymptomatic at-risk individuals... - Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, Abeta, and Alzheimer's diseaseMinerva M Carrasquillo
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America
PLoS ONE 5:e8764. 2010..The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD)... - BRI2 (ITM2b) inhibits Abeta deposition in vivoJungsu Kim
Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
J Neurosci 28:6030-6. 2008..These studies demonstrate that BRI2 is a novel mediator of Abeta deposition in vivo... - Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomainsSuzanne Wahrle
Department of Neuroscience and Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Neurobiol Dis 9:11-23. 2002..Thus, altering cholesterol levels may influence the development of Alzheimer's disease (AD) by influencing production and deposition of Abeta within cholesterol rich membrane microdomains... - Replication of CLU, CR1, and PICALM associations with alzheimer diseaseMinerva M Carrasquillo
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd, Birdsall Building, Jacksonville, FL 32224, USA
Arch Neurol 67:961-4. 2010..To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease... - Gene expression levels as endophenotypes in genome-wide association studies of Alzheimer diseaseF Zou
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neurology 74:480-6. 2010..Late-onset Alzheimer disease (LOAD) is a common disorder with a substantial genetic component. We postulate that many disease susceptibility variants act by altering gene expression levels... - Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's diseaseMinerva M Carrasquillo
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
Nat Genet 41:192-8. 2009..0 x 10(-7)) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41)... - Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's diseaseFanggeng Zou
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Hum Mol Genet 17:929-35. 2008..49, 95% confidence interval (CI) of 1.13-1.97, uncorrected P = 0.005], but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion... - Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretaseJoanna L Jankowsky
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hum Mol Genet 13:159-70. 2004..These data suggest that PS1 variants do not simply alter the preferred cleavage site for gamma-secretase, but rather that they have more complex effects on the regulation of gamma-secretase and its access to substrates... - Dimeric amyloid beta protein rapidly accumulates in lipid rafts followed by apolipoprotein E and phosphorylated tau accumulation in the Tg2576 mouse model of Alzheimer's diseaseTakeshi Kawarabayashi
Department of Neurology, Okayama University Graduate School of Medicine, Okayama, 700-8558, Japan
J Neurosci 24:3801-9. 2004..A similar increase in ApoE and a large increase in phosphorylated tau was observed in lipid rafts from AD brain. These findings suggest that lipid rafts may be an important site for interaction between dimeric Abeta, ApoE, and tau... - The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult micePaul H Wen
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
Exp Neurol 188:224-37. 2004..They also identify a new mechanism whereby PS1 FAD mutants may impair normal neuronal function and may have implications for the physiological functioning of the hippocampus in FAD... - Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouseEmily J H Lehman
Department of Genetics, Case Western Reserve University, and Center for Human Genetics, University Hospitals of Cleveland, OH 44106 4955, USA
Hum Mol Genet 12:2949-56. 2003.... - Identification of loci determining susceptibility to the lethal effects of amyloid precursor protein transgene overexpressionJoseph Krezowski
McLaughlin Research Institute, 1520 23rd Street South, Great Falls, MT 59405, USA
Hum Mol Genet 13:1989-97. 2004.... - Serum creatinine levels correlate with plasma amyloid Beta proteinZoe Arvanitakis
Rush University, Chicago, Illinois, USA
Alzheimer Dis Assoc Disord 16:187-90. 2002..01), accounting for 7.3% and 3.1% of shared variance, respectively. Significant associations were also present in NC and AD groups separately. These results indicate that it may be useful to consider Cr levels when measuring plasma Abeta... - Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's diseaseJoanna L Jankowsky
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 25:5217-24. 2005..These results demonstrate that the generation of Abeta in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors... - Cerebrovascular autoregulation is profoundly impaired in mice overexpressing amyloid precursor proteinKiyoshi Niwa
Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA
Am J Physiol Heart Circ Physiol 283:H315-23. 2002..The resulting alterations in cerebral perfusion may play a role in the brain dysfunction and periventricular white-matter changes associated with Alzheimer's dementia... - The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's diseaseMarcus A Westerman
Department of Neurology, Center for Clinical and Molecular Neurobiology, University of Minnesota, Minneapolis, Minnesota 55455, USA
J Neurosci 22:1858-67. 2002..These studies also provide a methodological framework within which to investigate these Abeta assemblies in vivo... - Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor proteinKiyoshi Niwa
Center for Clinical and Molecular Neurobiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
Neurobiol Dis 9:61-8. 2002..These observations support the hypothesis that cerebrovascular and metabolic abnormalities are early events in the pathogenesis of Alzheimer's disease... - BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's diseaseMasuo Ohno
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Neuron 41:27-33. 2004..Our gene-based approach demonstrates that lower Abeta levels are beneficial for AD-associated memory impairments, validating BACE1 as a therapeutic target for AD... - Lack of association of hepatic lipase polymorphisms with late-onset Alzheimer's diseaseHaiyan Zhu
Department of Physiology and Sanders Brown Center on Aging, University of Kentucky, 800 S Limestone St, Lexington, KY 40536 0230, USA
Neurobiol Aging 29:793-4. 2008..However, this association was not confirmed in two subsequent series based at the University of Kentucky (UKY, p=0.15) or the Mayo Clinic in Jacksonville (MCJ, p=0.97). Hence, rs6084 is not consistently associated with LOAD... - Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer diseaseJoanna L Jankowsky
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
PLoS Med 2:e355. 2005..However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis... - Cyclooxygenase-2 inhibition improves amyloid-beta-mediated suppression of memory and synaptic plasticityLinda A Kotilinek
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Brain 131:651-64. 2008..The results lead us to propose a third possible mechanism by which NSAIDs may protect against Alzheimer's disease, involving the blockade of a COX-2-mediated PGE2 response at synapses... - Type-specific evolution of amyloid plaque and angiopathy in APPsw miceYasuo Harigaya
Neurology Service, Maebashi Red Cross Hospital, 3 21 36 Asahi cho, Maebashi, Gunma 371 0014, Japan
Neurosci Lett 395:37-41. 2006.... - Plasmin deficiency does not alter endogenous murine amyloid beta levels in miceH Michael Tucker
Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, 800 S Limestone St, Lexington, KY 40536 0230, USA
Neurosci Lett 368:285-9. 2004..Hence, although plasmin is potentially important in the degradation of A beta aggregates, we interpret these data as suggesting that plasmin does not regulate steady-state A beta levels in non-pathologic conditions... - Rodent A beta modulates the solubility and distribution of amyloid deposits in transgenic miceJoanna L Jankowsky
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
J Biol Chem 282:22707-20. 2007..These findings suggest that, although mouse A beta does not influence the rate of amyloid formation, the incorporation of A beta peptides with differing sequences alters the solubility and localization of the resulting aggregates... - Bosentan preserves endothelial function in mice overexpressing APPAhmad A Elesber
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Neurobiol Aging 27:446-50. 2006..The current study demonstrates the presence of endothelial dysfunction in both carotid and aortic arteries in mice overexpressing APP and suggests a pathophysiological role for the endogenous endothelin system in AD...
Research Grants
- PLASMA A BETA AS A SURROGATE GENETIC MARKER FOR LOADSteven Younkin; Fiscal Year: 2005....
- ChAT, AChE, and Cholinergic Neurons in Aging and ADSteven Younkin; Fiscal Year: 2007..The utility of these additional biomarkers will be evaluated singly as compared to plasma Aft and jointly with plasma AB. ..
- ChAT, AChE, and Cholinergic Neurons in Aging and ADSteven Younkin; Fiscal Year: 2009..The utility of these additional biomarkers will be evaluated singly as compared to plasma Aft and jointly with plasma AB. ..
- Plasma AB as a Surrogate Genetic Marker for LOADSteven Younkin; Fiscal Year: 2009....
- ChAT, AChE, and Cholinergic Neurons in Aging and ADSteven G Younkin; Fiscal Year: 2010..The utility of these additional biomarkers will be evaluated singly as compared to plasma Aft and jointly with plasma AB. ..
- CHAT, ACHE, AND CHOLINERGIC NEURONS IN AGING AND ALZHEIMSteven Younkin; Fiscal Year: 2004..abstract_text> ..
- Plasma AB as a Surrogate Genetic Marker for LOADSteven G Younkin; Fiscal Year: 2010....