Research Topics
Species | E HeadSummaryAffiliation: University of Kentucky Country: USA Publications
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Detail Information
Publications
Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomersRakez Kayed
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
Mol Neurodegener 5:57. 2010..Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates...- A fibril-specific, conformation-dependent antibody recognizes a subset of Abeta plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brainFloyd Sarsoza
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697, USA
Acta Neuropathol 118:505-17. 2009.... - Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human agingE Head
Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, CA, USA
Exp Neurol 220:171-6. 2009..These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by behavioral enrichment... - Neurobiology of the aging dogElizabeth Head
Sanders Brown Center on Aging, Department of Molecular and Biomedical Pharmacology, University of Kentucky, 800 South Limestone Street, Lexington, KY 40536, USA
Age (Dordr) 33:485-96. 2011..Interestingly, the prefrontal cortex appears to be particularly vulnerable early in the aging process in dogs and this may be reflected in dysfunction in specific cognitive domains with age... - Plasma amyloid-β as a function of age, level of intellectual disability, and presence of dementia in Down syndromeElizabeth Head
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 40536, USA
J Alzheimers Dis 23:399-409. 2011..In summary, plasma Aβ can help predict cognitive function in adults with DS independently of the presence or absence of dementia... 
Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human agingM Y Su
Health Sciences Research Imaging Center, University of California, Irvine 92697, USA
Neurobiol Aging 19:479-85. 1998..These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions...- Clinical and pathological evidence for a frontal variant of Alzheimer diseaseJ K Johnson
Institute for Brain Aging and Dementia, University of California at Irvine, 92697 4285, USA
Arch Neurol 56:1233-9. 1999..We hypothesized that these patients would exhibit a greater degree of either neurofibrillary tangle (NFT) or senile plaque pathology in the frontal lobes than would patients with typical AD... - Visual-discrimination learning ability and beta-amyloid accumulation in the dogE Head
Institute for Brain Aging and Dementia, University of California, Irvine, 92697 4540, USA
Neurobiol Aging 19:415-25. 1998..The results of these studies support an association between cognitive test and the location and extent of beta-amyloid pathology... - Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological interventionE Head
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
J Alzheimers Dis 11:61-76. 2007..In combination, adults with DS may be a unique group of individuals well-suited for studies involving the manipulation or upregulation of compensatory responses as an approach to promote successful brain aging in the general population... - Correlation between caspase activation and neurofibrillary tangle formation in Alzheimer's diseaseT T Rohn
Institute for Brain Aging and Dementia, University of California at Irvine, 92697-4540, USA
Am J Pathol 158:189-98. 2001..84). Taken together, these results provide evidence for the activation of apoptotic mechanisms in neurons in the AD brain and suggest that there is an association between NFT formation and the activation of apoptotic pathways in AD... - Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down SyndromeE Head
Institute for Brain Aging and Dementia, University of California, Irvine, California 92697-4540, USA
Neurobiol Dis 8:252-65. 2001..C1q-positive neurons were associated with activated microglia. These results provide evidence for Abeta-mediated inflammatory factors contributing to the rapid accumulation of neuropathology in DS brain... - Neuroimaging of individuals with Down's syndrome at-risk for dementia: evidence for possible compensatory eventsR J Haier
Department of Pediatrics, University of California, Irvine 92697 4475, USA
Neuroimage 39:1324-32. 2008..We report functional and structural brain indicators that may precede the onset of dementia in individuals with Down's syndrome (DS)... - Oxidation of Abeta and plaque biogenesis in Alzheimer's disease and Down syndromeE Head
Institute for Brain Aging and Dementia, University of California, Irvine, California, 92697-4540, USA
Neurobiol Dis 8:792-806. 2001..Oxidatively modified Abeta may reflect the efforts of microglial cells to take up and degrade Abeta. Oxidative modification of Abeta may be an early event in Abeta pathogenesis and may be important for plaque biogenesis... - Region-specific age at onset of beta-amyloid in dogsE Head
Institute for Brain Aging and Dementia, University of California, Research Faculty, 1226 Gillespie Neuroscience, Irvine, CA 92697 4540, USA
Neurobiol Aging 21:89-96. 2000..We propose that these models will be a useful tool to evaluate interventions that delay the age of onset or slow the rate of accumulation of Abeta in the dog... - Beta-amyloid deposition and tau phosphorylation in clinically characterized aged catsE Head
Department of Neurology, Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
Neurobiol Aging 26:749-63. 2005..Thus, the aged cat brain develops AD-related lesions with important morphological and biochemical differences compared to human brain... - Down syndrome and Alzheimer's disease: a link between development and agingI T Lott
Department of Pediatrics, University of California, Irvine, Orange, CA 92868, USA
Ment Retard Dev Disabil Res Rev 7:172-8. 2001..Study of the process by which AD evolves in DS affords an opportunity to understand an important link between development and aging. This review will focus on advances in the molecular and clinical basis of this association... - Initiation and propagation of molecular cascades in human brain aging: insight from the canine model to promote successful agingE Head
Institute for Brain Aging and Dementia, University of California Irvine, 92697 4540, USA
Prog Neuropsychopharmacol Biol Psychiatry 24:777-86. 2000..The dog can serve as a useful model for interventions during the initiation stage since dogs develop neuropathology that closely resembles that observed in high pathology human brains... - The canine as an animal model of human aging and dementiaB J Cummings
Brain Aging Institute, University of California, Irvine 92717 4540, USA
Neurobiol Aging 17:259-68. 1996..These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation... - Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brainM Nistor
Institute for Brain Aging and Dementia, CA, United States
Neurobiol Aging 28:1493-506. 2007..Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Abeta degradation and clearance... - Temporal cortex hypermetabolism in Down syndrome prior to the onset of dementiaR J Haier
Department of Pediatrics, University of California, Irvine 92697 5000, USA
Neurology 61:1673-9. 2003.... - Amyloid-beta peptide and oligomers in the brain and cerebrospinal fluid of aged caninesElizabeth Head
Department of Molecular and Biomedical Pharmacology and the Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536 0230, USA
J Alzheimers Dis 20:637-46. 2010.... 
Changes in cognition and amyloid-β processing with long term cholesterol reduction using atorvastatin in aged dogsM Paul Murphy
Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 405360230, USA
J Alzheimers Dis 22:135-50. 2010....- Oxidative damage increases with age in a canine model of human brain agingE Head
Institute for Brain Aging and Dementia, University of California, Irvine, California 92697 4540, USA
J Neurochem 82:375-81. 2002..This evidence of widespread oxidative damage and Abeta deposition is further justification for using the canine model for studying human brain aging and neurodegenerative diseases... - A two-year study with fibrillar beta-amyloid (Abeta) immunization in aged canines: effects on cognitive function and brain AbetaElizabeth Head
Institute for Brain Aging and Dementia, and Department of Neurology, University of California, Irvine, Irvine, California 92697, USA
J Neurosci 28:3555-66. 2008..Alternatively, clearing preexisting Abeta from the brain in a treatment study may be more efficacious for cognition if combined with a second intervention that restores neuron health... - Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndromeE Head
Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
J Neuropathol Exp Neurol 62:917-26. 2003..Thus, compensatory growth responses may occur in DS prior to extensive AD pathology and may be one mechanism underlying observations in PET studies of hypermetabolism in the entorhinal cortex of individuals with DS... - Synergistic effects of long-term antioxidant diet and behavioral enrichment on beta-amyloid load and non-amyloidogenic processing in aged caninesViorela Pop
Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
J Neurosci 30:9831-9. 2010..Overall, the data indicate that multidomain treatments may be a valuable intervention strategy to reduce neuropathology and improve cognitive function in humans... - Region specific neuron loss in the aged canine hippocampus is reduced by enrichmentChristina T Siwak-Tapp
Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
Neurobiol Aging 29:39-50. 2008..These results suggest that the aged canine hippocampus in the left hemisphere shows selective neuron loss and that behavioral enrichment may reduce this loss... - Immunization with fibrillar Abeta(1-42) in young and aged canines: Antibody generation and characteristics, and effects on CSF and brain AbetaElizabeth Head
Institute for Brain Aging and Dementia, Department of Neurology, University of California, 1259 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
Vaccine 24:2824-34. 2006..A nonsignificant increase in CSF Abeta(1-40) and decrease in Abeta(1-40/1-42) in cortex was detected. Canines may be a useful system for testing an Abeta vaccine... - Linear and conformation specific antibodies in aged beagles after prolonged vaccination with aggregated AbetaVitaly Vasilevko
The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697 4540, USA
Neurobiol Dis 39:301-10. 2010..Our findings indicate that prolonged immunization results in distinctive temporal changes in antibody profiles, which may be important for other experimental and clinical settings... - Accumulation of caspase cleaved amyloid precursor protein represents an early neurodegenerative event in aging and in Alzheimer's diseaseMing Zhao
Institute for Brain Aging and Dementia, University of California Irvine, Irvine, CA 92697-4540, USA
Neurobiol Dis 14:391-403. 2003..These findings raise the possibility that the activation of caspase-3 and cleavage of APP may be involved with neuronal degeneration and that pathways characteristic of apoptosis are activated in AD... - Immunotherapy in a natural model of Abeta pathogenesis: the aging beagleVitaly Vasilevko
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
CNS Neurol Disord Drug Targets 8:98-113. 2009..We propose that the canine model complements existing animal models and will be helpful in developing new vaccine approaches to slowing or preventing Abeta pathology that can be translated to human clinical trials... - Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunctionCarl W Cotman
Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
Neurobiol Aging 23:809-18. 2002..Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies... - The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approachesCarl W Cotman
Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, CA 92697 4540, USA
J Alzheimers Dis 15:685-707. 2008..In addition, combinatorial treatment approaches can be a powerful strategy for improving brain function through enhancement of multiple molecular pathways... - Oxidative damage and cognitive dysfunction: antioxidant treatments to promote healthy brain agingElizabeth Head
Department of Neurology, Institute for Brain Aging and Dementia, University of California, 1259 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
Neurochem Res 34:670-8. 2009..In combination, antioxidants may be beneficial for promoting healthy brain aging and reducing the risk of neurodegenerative disease... - Effects of scopolamine challenge on regional cerebral blood volume. A pharmacological model to validate the use of contrast enhanced magnetic resonance imaging to assess cerebral blood volume in a canine model of agingP Dwight Tapp
John Tu and Thomas Yuen Center for Functional Onco-Imaging, University of California, 164 Irvine Hall, Irvine, CA, USA
Prog Neuropsychopharmacol Biol Psychiatry 29:399-406. 2005.... - Oxidative stress, aging, and central nervous system disease in the canine model of human brain agingElizabeth Head
Institute for Brain Aging and Dementia, Department of Neurology, University of California at Irvine, 1259 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
Vet Clin North Am Small Anim Pract 38:167-78, vi. 2008..Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs... - Nutraceuticals, aging, and cognitive dysfunctionElizabeth Head
Institute for Brain Aging and Dementia, University of California at Irvine, 1259 Gillespie NRF, Irvine, CA 92697 4540, USA
Vet Clin North Am Small Anim Pract 34:217-28. 2004.... - Application of an automated voxel-based morphometry technique to assess regional gray and white matter brain atrophy in a canine model of agingP Dwight Tapp
John Tu and Thomas Yuen Center for Functional Onco Imaging, University of California, 164 Irvine Hall, Irvine, CA 92697 5020, USA
Neuroimage 29:234-44. 2006.... - Beta-amyloid, oxidative stress and down syndromeIra T Lott
Department of Pediatrics and Neurology, Alzheimer Disease Research Center, University of California, Irvine, School of Medicine, Irvine, California 92868, USA
Curr Alzheimer Res 3:521-8. 2006..Since the pathological processes leading to AD are seen across the lifespan in DS, an opportunity is afforded for early pharmacological intervention in the disorder... - Learning and memory as a function of age in Down syndrome: a study using animal-based tasksLinda Nelson
Department of Neurology, University of California, Irvine, Medical Center, 101 City Drive, Route 81, Building 53, Room 225, Orange, CA 92868, USA
Prog Neuropsychopharmacol Biol Psychiatry 29:443-53. 2005..These changes may reflect prefrontal and medial temporal lobe dysfunction that is associated with the development of AD pathology in DS... - Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive functionChristina T Siwak-Tapp
Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
Neurobiol Learn Mem 88:249-59. 2007..These results suggest that new neurons in the aged canine dentate gyrus may participate in modulating cognitive functions... - Combining an antioxidant-fortified diet with behavioral enrichment leads to cognitive improvement and reduced brain pathology in aging canines: strategies for healthy agingElizabeth Head
Institute for Brain Aging and Dementia, Department of Neurology, University of California at Irvine, 1259 Gillespie NRF, Irvine, CA 92697 4540, USA
Ann N Y Acad Sci 1114:398-406. 2007..These results suggest that modifying lifestyle factors can have a beneficial impact on the aging process, even in aged individuals with existing cognitive decline and brain pathology... - Insights into Abeta and presenilin from a canine model of human brain agingElizabeth Head
Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, California 92697 4540, USA
Neurobiol Dis 9:1-10. 2002..These in vivo observations suggest a common site for both Abeta and presenilin supporting the hypothesis that the latter is involved with APP processing... - Spatial patterns of mammalian brain aging: distribution of cathepsin D-immunoreactive cell bodies and dystrophic dendrites in aging dogs resembles that in Alzheimer's diseaseXiaoning Bi
Department of Psychiatry and Human Behavior, University of California at Irvine, Irvine, California 92697, USA
J Comp Neurol 464:371-81. 2003..Combined with previous results for rats, these findings indicated that changes in cathepsin D observed in AD, in particular in the temporal lobe, reflect a generalized mammalian pattern of brain aging... - Caspase-cleaved amyloid precursor protein and activated caspase-3 are co-localized in the granules of granulovacuolar degeneration in Alzheimer's disease and Down's syndrome brainJoseph H Su
Institute for Brain Aging and Dementia, University of California at Irvine, 92697 4540, USA
Acta Neuropathol 104:1-6. 2002..A caspase-cleavage product of fodrin that accumulates in many AD and DS neurons is not present in GVD granules. These data support a role for the activation of apoptotic mechanisms in selective compartments exhibiting GVD... - Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and down syndrome dementiaPinar E Coskun
Mitochondrial and Molecular Medicine and Genetics, University of California Irvine, Irvine, CA, USA
J Alzheimers Dis 20:S293-310. 2010..Therefore, mtDNA alterations may be responsible for both age-related dementia and the associated neuropathological changes observed in AD and DSAD... - Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acidJiankang Liu
Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA
Proc Natl Acad Sci U S A 99:2356-61. 2002..These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function... - Aging and cerebrovascular dysfunction: contribution of hypertension, cerebral amyloid angiopathy, and immunotherapyVitaly Vasilevko
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA
Ann N Y Acad Sci 1207:58-70. 2010..Thus, there is a critical need for new strategies that improve BBB function and limit the development of β-amyloidosis in the cerebral vasculature... - Common structure of soluble amyloid oligomers implies common mechanism of pathogenesisRakez Kayed
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
Science 300:486-9. 2003..These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity... - Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunctionJennifer L Tomic
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697 3900, USA
Neurobiol Dis 35:352-8. 2009..These results indicate that fibrillar oligomers may play a key role in the pathology of AD and may be a new target for diagnostic and therapeutic development... - APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest oldDaniel J Berlau
Institute of Brain Aging and Dementia, University of California Irvine, Irvine, CA 92697 1400, USA
Neurology 72:829-34. 2009..This would predict, even with advanced age, that APOE2 carriers would be less likely to have dementia and less likely to meet pathologic criteria for AD... - Down syndrome and beta-amyloid depositionElizabeth Head
Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, California, USA
Curr Opin Neurol 17:95-100. 2004..The purpose of the current review is therefore to summarize developments and advances in our understanding of beta-amyloid pathogenesis in Down syndrome over the past year... - Gene expression changes in the course of normal brain aging are sexually dimorphicNicole C Berchtold
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
Proc Natl Acad Sci U S A 105:15605-10. 2008.... - Rhinal and dorsolateral prefrontal cortex lesions produce selective impairments in object and spatial learning and memory in caninesLori Ann Christie
Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
J Comp Neurol 511:257-70. 2008.... - Synaptic proteins, neuropathology and cognitive status in the oldest-oldElizabeth Head
Institute of Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
Neurobiol Aging 30:1125-34. 2009..Frontal cortex SYN protein levels may protect neuronal function in oldest-old individuals and reflect compensatory responses that may be involved with maintaining cognition... - Alzheimer's disease peptide epitope vaccine reduces insoluble but not soluble/oligomeric Abeta species in amyloid precursor protein transgenic miceIrina Petrushina
The Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
J Neurosci 27:12721-31. 2007.... - Annular protofibrils are a structurally and functionally distinct type of amyloid oligomerRakez Kayed
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
J Biol Chem 284:4230-7. 2009..The annular anti-protofibril antibody also recognizes heptameric alpha-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a beta barrel structural motif...
Research Grants
- Beta-Amyloid Immunization in a Canine Model of AgingElizabeth Head; Fiscal Year: 2010....
- Aging of Frontal Structure and Function in Down Syndrome and DementiaFrederick Schmitt; Fiscal Year: 2010..Treatments for AD in DS will be more effective if the disease is detected early, and identifying biomarkers will greatly facilitate the development of therapeutics. ..