L C Walker
Affiliation: Pfizer Global Research and Development
- Proteopathy: the next therapeutic frontier?Lary C Walker
CNS Pharmacology, Pfizer Ann Arbor Laboratories, MI 48105, USA
Curr Opin Investig Drugs 3:782-7. 2002..Our present knowledge suggests three broad therapeutic approaches to abrogating the proteopathic cascade: reduce the production of the offending proteins, prevent their self-assembly, or promote their removal...
- Modeling Alzheimer's disease and other proteopathies in vivo: is seeding the key?L C Walker
CNS Pharmacology, Pfizer Ann Arbor Laboratories, Ann Arbor, Michigan 48105, USA
Amino Acids 23:87-93. 2002....
- Exogenous induction of cerebral beta-amyloidosis in betaAPP-transgenic miceLary C Walker
CNS Pharmacology, Pfizer Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
Peptides 23:1241-7. 2002..The AD-seeding model can illuminate the emergence and spread of cerebral beta-amyloidosis and tau hyperphosphorylation, and thus could enhance our understanding of AD and its pathogenic commonalties with other cerebral proteopathies...
- Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic miceM J Callahan
Neuroscience Therapeutics, Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Rd, Ann Arbor, MI 48105, USA
Am J Pathol 158:1173-7. 2001..These data show that senescent female Tg2576 mice deposit more amyloid in the brain than do male mice, and may provide an animal model in which the influence of sex differences on cerebral amyloid pathology can be evaluated...
- Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic miceM D Kane
Neuroscience Therapeutics, Parke Davis Research, Division of Warner Lambert, Ann Arbor, Michigan 48105, USA
J Neurosci 20:3606-11. 2000..The paradigm can be used to clarify the conditions that initiate in vivo beta-amyloidogenesis in the brain and may yield a more authentic animal model of Alzheimer's disease and other neurodegenerative disorders...
- Apolipoprotein E4 promotes the early deposition of Abeta42 and then Abeta40 in the elderlyL C Walker
Neuroscience Therapeutics, Parke Davis Pharmaceutical Research, Division of Warner Lambert, Ann Arbor, MI 48105, USA
Acta Neuropathol 100:36-42. 2000..We conclude that ApoEepsilon4 hastens the onset of Abeta42 deposition in the senescent brain, which in turn fosters the earlier evolution of fibrillar, Abeta40-positive plaques, thereby increasing the risk of Alzheimer's disease...
- Animal models of cerebral beta-amyloid angiopathyL C Walker
Parke Davis Pharmaceutical Research, Division of Warner Lambert, Ann Arbor, MI 48105, USA
Brain Res Brain Res Rev 25:70-84. 1997..The existing animal models have shown considerable utility in deciphering the pathobiology of CAA, and in testing strategies that could be used to diagnose and treat this disorder in humans...
- Cerebrovascular amyloidosis: experimental analysis in vitro and in vivoL C Walker
Parke Davis Pharmaceutical Research Division, Warner Lambert Co, Ann Arbor, MI 48105, USA
Histol Histopathol 14:827-37. 1999..Methods for delivering agents selectively to vascular amyloid in living subjects are now being developed, and these techniques are paving the way to the development of diagnostic tools and therapies for cerebrovascular amyloidosis...
- Cerebral lipid deposition in aged apolipoprotein-E-deficient miceL C Walker
Department of Neurological and Neurodegenerative Disorders, Division of Warner Lambert Co, Ann Arbor, Michigan 48105, USA
Am J Pathol 151:1371-7. 1997..It may be fruitful to seek potential interactions between genetic factors and diet in modulating the risk of Alzheimer's disease and other neurodegenerative disorders in aged humans...
- Development of transgenic rats producing human beta-amyloid precursor protein as a model for Alzheimer's disease: transgene and endogenous APP genes are regulated tissue-specificallyCansu Agca
University of Missouri College of Veterinary Medicine, Department of Veterinary Pathobiology Columbia, MO 65211, USA
BMC Neurosci 9:28. 2008..Some instances of FAD have been linked to mutations in the beta-amyloid protein precursor (APP). Although there are numerous mouse AD models available, few rat AD models, which have several advantages over mice, have been generated...
- Tauopathy with paired helical filaments in an aged chimpanzeeRebecca F Rosen
Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
J Comp Neurol 509:259-70. 2008....
- Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and hostMelanie Meyer-Luehmann
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D 72076 Tubingen, Germany
Science 313:1781-4. 2006..The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains...
- Inducible proteopathiesLary C Walker
Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA 30322, USA
Trends Neurosci 29:438-43. 2006....
- Emerging prospects for the disease-modifying treatment of Alzheimer's diseaseLary C Walker
Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30322, USA
Biochem Pharmacol 69:1001-8. 2005..These adverse events were not anticipated from preclinical studies with rodents; hence, more biologically relevant models, such as nonhuman primates, are needed to test the safety and efficacy of novel therapies for Alzheimer's disease...
- Clinico-pathologic function of cerebral ABC transporters - implications for the pathogenesis of Alzheimer's diseaseJens Pahnke
University of Rostock, Department of Neurology, Neurodegeneration Research Laboratory NRL, Gehlsheimer Str 20, 18147 Rostock, Germany
Curr Alzheimer Res 5:396-405. 2008..Here, we summarize findings from cell culture experiments, animal models and studies of patients with Alzheimer's disease. Furthermore, we discuss pharmacological interactions and computational methods for risk assessment...
- Aging, gender and APOE isotype modulate metabolism of Alzheimer's Abeta peptides and F-isoprostanes in the absence of detectable amyloid depositsJun Yao
Department of Psychiatry, New York University, The Nathan S Kline Institute for Psychiatric Research, Orangeburg, New York, USA
J Neurochem 90:1011-8. 2004....
- Axonopathy, tau abnormalities, and dyskinesia, but no neurofibrillary tangles in p25-transgenic miceFeng Bian
CNS Pharmacology, Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
J Comp Neurol 446:257-66. 2002....
- Long-term hypothermia reduces infarct volume in aged rats after focal ischemiaBaltromejus Florian
Department of Neurology, University of Greifswald, Ellernholzstr 1 2, 17487 Greifswald, Germany
Neurosci Lett 438:180-5. 2008..Behaviorally, hypothermia was associated with better performance on tests that require complex sensorimotor skills, in the absence of obvious neurological deficits or physiological side effects, in aged rats...
- Deposition of Alzheimer's beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humansSilke Vogelgesang
Departments of Neuropathology and Pharmacology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, University of Greifswald, Greifswald, Germany
Pharmacogenetics 12:535-41. 2002..Our results provide the first evidence in human brain tissue that the accumulation of Abeta may be influenced by the expression of P-gp in blood vessels, and suggest that P-gp may influence the elimination of Abeta from brain...
- The response of the aged brain to stroke: too much, too soon?Aurel Popa-Wagner
Department of Neurology, University of Greifswald, Greifswald, Germany
Curr Neurovasc Res 4:216-27. 2007..Elucidating the molecular basis of this phenomenon in the aging brain could yield novel approaches to neurorestoration following stroke or head injury in the elderly...
- MDR1-P-Glycoprotein (ABCB1) Mediates Transport of Alzheimer's amyloid-beta peptides--implications for the mechanisms of Abeta clearance at the blood-brain barrierDiana Kuhnke
Department of Pharmacology, Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany
Brain Pathol 17:347-53. 2007..Our data support the concept that P-gp is important for the clearance of Abeta from brain, and thus may represent a target protein for the prevention and/or treatment of neurodegenerative disorders such as AD...
- Alzheimer's Abeta vaccination of rhesus monkeys (Macaca mulatta)Sam Gandy
Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA
Mech Ageing Dev 125:149-51. 2004..These data support the use of non-human primates to model certain phenomena associated with vaccination of humans with aggregated Alzheimer's Abeta...
- Alzheimer A beta vaccination of rhesus monkeys (Macaca mulatta)Sam Gandy
Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut St, Suite 467, Philadelphia, PA 19107, USA
Alzheimer Dis Assoc Disord 18:44-6. 2004..These data support the use of nonhuman primates to model certain phenomena associated with vaccination of humans with aggregated Alzheimer A beta...
- Alzheimer therapeutics-what after the cholinesterase inhibitors?Lary C Walker
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA
Age Ageing 35:332-5. 2006
- Cerebrovascular P-glycoprotein expression is decreased in Creutzfeldt-Jakob diseaseSilke Vogelgesang
Department of Neuropathology, University of Greifswald, 17487, Greifswald, Germany
Acta Neuropathol 111:436-43. 2006....
- The role of P-glycoprotein in cerebral amyloid angiopathy; implications for the early pathogenesis of Alzheimer's diseaseSilke Vogelgesang
Department of Neuropathology, University of Greifswald, Germany
Curr Alzheimer Res 1:121-5. 2004..The impairment of Abeta clearance could lead to the accumulation and earlier deposition of Abeta, both in the walls of blood vessels and in the brain parenchyma, thus elevating the risk of CAA and AD...
- Proteomic identification of the involvement of the mitochondrial rieske protein in epilepsyHeike Junker
Institutes of Biochemistry, Ernst Moritz Arndt University, Greifswald, Germany
Epilepsia 46:339-43. 2005....