The Value of Transgenic Models for the Study of Neurodegenerative Diseases

Abstract: Transgenic animal models are useful in studying the features of APP‐ and PS1‐linked FAD and SOD1‐linked FALS. These models help to investigate the nature of the cellular/biochemical/molecular alterations in neural tissue; the character and evolution of neuronal and/or glial abnormalities; the ways mutant proteins cause damage to neurons; and the biochemical pathways associated with cell death. New technologies will help to define changes in a variety of genes/gene products and the events and conformational changes in mutant proteins that are implicated in pathogenic cascades. It is hoped such study will result in novel treatments for testing in transgenic models that can then be translated into new treatments for human neurodegenerative diseases.

[1]  S. W. Davies,et al.  Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice , 1996, Cell.

[2]  M. Gurney,et al.  Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis , 1998, Annals of neurology.

[3]  J. Hardy,et al.  Alzheimer's disease: In search of γ-secretase , 1999, Nature.

[4]  Q. Zhu,et al.  Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  V. Culotta,et al.  Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Selkoe,et al.  Translating cell biology into therapeutic advances in Alzheimer's disease , 1999, Nature.

[7]  R. Motter,et al.  Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse , 1999, Nature.

[8]  D. Borchelt,et al.  ALS-Linked SOD1 Mutant G85R Mediates Damage to Astrocytes and Promotes Rapidly Progressive Disease with SOD1-Containing Inclusions , 1997, Neuron.

[9]  Mark Turmaine,et al.  Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation , 1997, Cell.

[10]  Robert H. Brown,et al.  Increased 3‐nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis , 1997, Annals of neurology.

[11]  Robert H. Brown,et al.  Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis , 1997, Journal of neurochemistry.

[12]  Robert H. Brown,et al.  Amyotrophic lateral sclerosis. Insights from genetics. , 1997, Archives of neurology.

[13]  M. Gurney,et al.  The Copper Chelator d‐Penicillamine Delays Onset of Disease and Extends Survival in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis , 1997, The European journal of neuroscience.

[14]  S. Prusiner,et al.  Doxycycline control of prion protein transgene expression modulates prion disease in mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Selkoe,et al.  Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity , 1999, Nature.

[16]  P. Wong,et al.  Pathogenesis of two axonopathies does not require axonal neurofilaments , 1998, Nature.

[17]  S. Tonegawa,et al.  Skeletal and CNS Defects in Presenilin-1-Deficient Mice , 1997, Cell.

[18]  D. Price,et al.  Loss of the Presynaptic Vesicle Protein Synaptophysin in Hippocampus Correlates with Cognitive Decline in Alzheimer Disease , 1997, Journal of neuropathology and experimental neurology.

[19]  J. Hardy,et al.  Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes , 1998, Nature Medicine.

[20]  P N Leigh,et al.  Excitotoxicity in ALS , 1996, Neurology.

[21]  M. Jackson,et al.  Gene expression profiles of laser-captured adjacent neuronal subtypes , 1999, Nature Medicine.

[22]  C. van Broeckhoven,et al.  Molecular genetics of Alzheimer's disease. , 1998, Annals of medicine.

[23]  D. Cleveland From Charcot to SOD1 Mechanisms of Selective Motor Neuron Death in ALS , 1999, Neuron.

[24]  J. Hardy,et al.  Genetic classification of primary neurodegenerative disease. , 1998, Science.

[25]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[26]  D. Borchelt,et al.  Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. , 1999, Human molecular genetics.

[27]  D. Borchelt,et al.  Motor neuron disease caused by mutations in superoxide dismutase 1. , 1995, Current opinion in neurology.

[28]  Bruce A. Yankner,et al.  Aging renders the brain vulnerable to amyloid β-protein neurotoxicity , 1998, Nature Medicine.

[29]  S. Carpenter Proximal axonal enlargement in motor neuron disease , 1968, Neurology.

[30]  L. Liotta,et al.  Immuno-LCM: laser capture microdissection of immunostained frozen sections for mRNA analysis. , 1999, The American journal of pathology.

[31]  Andreas Weidemann,et al.  Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein , 1989, Cell.

[32]  J. Julien,et al.  Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: A mouse model of amyotrophic lateral sclerosis , 1993, Cell.

[33]  M. Albert,et al.  Cognitive and neurobiologic markers of early Alzheimer disease. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  L. Liotta,et al.  Laser-capture microdissection: opening the microscopic frontier to molecular analysis. , 1998, Trends in genetics : TIG.

[35]  J. Morris,et al.  Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease , 1999, Annals of neurology.

[36]  A. Peterson,et al.  Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-β-galactosidase fusion protein , 1994, Neuron.

[37]  M. Gurney,et al.  Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. , 1994, The American journal of pathology.

[38]  J. Morrison,et al.  Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[39]  D. Price,et al.  The Copper Chaperone CCS Is Abundant in Neurons and Astrocytes in Human and Rodent Brain , 1999, Journal of neurochemistry.

[40]  D. Borchelt,et al.  Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[41]  S. Lippard Free Copper Ions in the Cell? , 1999, Science.

[42]  R. Casareno,et al.  The Copper Chaperone for Superoxide Dismutase* , 1997, The Journal of Biological Chemistry.

[43]  D L Price,et al.  Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Gurney,et al.  A low expressor line of transgenic mice carrying a mutant human Cu,Zn superoxide dismutase (SOD1) gene develops pathological changes that most closely resemble those in human amyotrophic lateral sclerosis , 1997, Acta Neuropathologica.

[45]  Í. Lopes-Cendes,et al.  The Neuropathology of CAG Repeat Diseases: Review and Update of Genetic and Molecular Features , 1997, Brain pathology.

[46]  Rainer M. Bohle,et al.  Real-time quantitative RT–PCR after laser-assisted cell picking , 1998, Nature Medicine.

[47]  Junying Yuan,et al.  Inhibition of ICE slows ALS in mice , 1997, Nature.

[48]  M. Pericak-Vance,et al.  Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. , 1993, Science.

[49]  H. Zoghbi,et al.  Expanding Our Understanding of Polyglutamine Diseases through Mouse Models , 1999, Neuron.

[50]  D. Price,et al.  Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues , 1996, The Journal of Neuroscience.

[51]  D L Price,et al.  Genetic neurodegenerative diseases: the human illness and transgenic models. , 1998, Science.

[52]  Bin Zhang,et al.  Age-Dependent Emergence and Progression of a Tauopathy in Transgenic Mice Overexpressing the Shortest Human Tau Isoform , 1999, Neuron.

[53]  D. Borchelt,et al.  Endoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives In Vivo , 1996, Neuron.

[54]  D. Westaway,et al.  Alzheimer's disease: Antibody clears senile plaques , 1999, Nature.

[55]  Ole A. Andreassen,et al.  Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis , 1999, Nature Medicine.

[56]  M. H. Angelis,et al.  Maintenance of somite borders in mice requires the Delta homologue Dll1 , 1997, Nature.

[57]  M. Gurney,et al.  Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. , 1994, Science.

[58]  P. Lansbury Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[59]  E. Stadtman Protein oxidation and aging , 2006, Science.

[60]  M. Mesulam Neuroplasticity Failure in Alzheimer's Disease Bridging the Gap between Plaques and Tangles , 1999, Neuron.

[61]  O. Puciłowski,et al.  [Neurotransmitters and neuropeptides]. , 1983, Polski tygodnik lekarski.

[62]  J. Morrison,et al.  Time course of neuropathology in the spinal cord of G86R superoxide dismutase transgenic mice , 1998, The Journal of comparative neurology.

[63]  J. Elliott Experimental Models of Amyotrophic Lateral Sclerosis , 1999, Neurobiology of Disease.

[64]  B. Sommer,et al.  Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[65]  S. Younkin,et al.  An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. , 1994, Science.

[66]  D. Borchelt,et al.  Axonal Transport of Mutant Superoxide Dismutase 1 and Focal Axonal Abnormalities in the Proximal Axons of Transgenic Mice , 1998, Neurobiology of Disease.

[67]  S. Sisodia Beta-amyloid precursor protein cleavage by a membrane-bound protease. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Hugo Vanderstichele,et al.  Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein , 1998, Nature.

[69]  E. Kandel,et al.  Inducible and Reversible Gene Expression with the rtTA System for the Study of Memory , 1998, Neuron.

[70]  J. Trojanowski,et al.  Neurofilaments and Orthograde Transport Are Reduced in Ventral Root Axons of Transgenic Mice that Express Human SOD1 with a G93A Mutation , 1997, The Journal of cell biology.

[71]  B. Hyman,et al.  APPSW Transgenic Mice Develop Age‐related Aβ Deposits and Neuropil Abnormalities, but no Neuronal Loss in CA1 , 1997, Journal of neuropathology and experimental neurology.

[72]  T. O’Halloran,et al.  Multiple Protein Domains Contribute to the Action of the Copper Chaperone for Superoxide Dismutase* , 1999, The Journal of Biological Chemistry.

[73]  D. Price,et al.  The genetic and molecular mechanisms of motor neuron disease , 1998, Current Opinion in Neurobiology.

[74]  D. Borchelt,et al.  Corrigendum: Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin (Human Molecular Genetics (1999) 8 (397-407)) , 1999 .

[75]  D. Bredesen,et al.  Altered Reactivity of Superoxide Dismutase in Familial Amyotrophic Lateral Sclerosis , 1996, Science.

[76]  E. Stadtman,et al.  A gain-of-function of an amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutant: An enhancement of free radical formation due to a decrease in Km for hydrogen peroxide. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[77]  I. Fridovich,et al.  Superoxide dismutases. , 1975, Annual review of biochemistry.

[78]  M. Mattson,et al.  Protein modification by the lipid peroxidation product 4‐hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients , 1998, Annals of neurology.

[79]  S. Younkin,et al.  Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice , 1996, Science.

[80]  J. Haines,et al.  Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis , 1993, Nature.

[81]  D. Price,et al.  Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing. , 1990, Science.

[82]  John Hardy,et al.  Amyloid, the presenilins and Alzheimer's disease , 1997, Trends in Neurosciences.

[83]  M. Dubois‐Dauphin,et al.  Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. , 1997, Science.

[84]  D. Borchelt,et al.  An Alzheimer's Disease-Linked PS1 Variant Rescues the Developmental Abnormalities of PS1-Deficient Embryos , 1998, Neuron.

[85]  D. Borchelt,et al.  Accelerated Amyloid Deposition in the Brains of Transgenic Mice Coexpressing Mutant Presenilin 1 and Amyloid Precursor Proteins , 1997, Neuron.

[86]  Harry T Orr,et al.  SCA1 transgenic mice: A model for neurodegeneration caused by an expanded CAG trinucleotide repeat , 1995, Cell.

[87]  J. Morrison,et al.  Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice: Neurochemical correlates of selective vulnerability , 1996, The Journal of comparative neurology.

[88]  L. WilliamsonT,et al.  神経フィラメントの欠如は,家族性筋萎縮性側索硬化症関連スーパオキジドジスムターゼ1変異に対する運動ニューロンの選択的易損性を低下させ,疾患を遅らせる , 1998 .

[89]  J. Gitlin,et al.  The Role of Copper in Neurodegenerative Disease , 1999, Neurobiology of Disease.

[90]  M. Gurney,et al.  Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[91]  J. Rossant,et al.  Notch1 is required for the coordinate segmentation of somites. , 1995, Development.

[92]  B. Sommer,et al.  Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[93]  D L Price,et al.  A vector for expressing foreign genes in the brains and hearts of transgenic mice. , 1996, Genetic analysis : biomolecular engineering.

[94]  D. Price,et al.  Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[95]  T. O’Halloran,et al.  Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. , 1999, Science.

[96]  G. Perry,et al.  Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[97]  L. Bruijn,et al.  Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. , 1998, Science.

[98]  J. Kong,et al.  Massive Mitochondrial Degeneration in Motor Neurons Triggers the Onset of Amyotrophic Lateral Sclerosis in Mice Expressing a Mutant SOD1 , 1998, The Journal of Neuroscience.

[99]  Jean-Pierre Julien,et al.  Neurofilament functions in health and disease , 1999, Current Opinion in Neurobiology.

[100]  D. Borchelt,et al.  Effects of PS1 Deficiency on Membrane Protein Trafficking in Neurons , 1998, Neuron.

[101]  Richard A. Smith Handbook of Amyotrophic Lateral Sclerosis , 1992 .

[102]  D. Price,et al.  Amyloid precursor protein in aged nonhuman primates. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[103]  G. Dawson,et al.  β-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity , 1995, Cell.

[104]  J. Gitlin,et al.  Genetic and molecular basis for copper toxicity. , 1996, The American journal of clinical nutrition.

[105]  D. Cleveland,et al.  Slowing of axonal transport is a very early event in the toxicity of ALS–linked SOD1 mutants to motor neurons , 1999 .

[106]  M. Gurney,et al.  Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis , 1996, Annals of neurology.

[107]  M. Beal,et al.  Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury , 1996, Nature Genetics.

[108]  D. Borchelt,et al.  An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria , 1995, Neuron.

[109]  D. Price,et al.  Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[110]  L. Mucke,et al.  Comparison of Neurodegenerative Pathology in Transgenic Mice Overexpressing V717F β-Amyloid Precursor Protein and Alzheimer’s Disease , 1996, The Journal of Neuroscience.

[111]  R. Barbour,et al.  Purification and cloning of amyloid precursor protein β-secretase from human brain , 1999, Nature.

[112]  A. Delacourte,et al.  The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease , 1999, Neurology.

[113]  J. Coyle,et al.  Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. , 1982, Science.

[114]  D. Price,et al.  Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm , 1997, Nature.

[115]  Alfredo G. Tomasselli,et al.  Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity , 1999, Nature.

[116]  A. Wernimont,et al.  Crystal structure of the copper chaperone for superoxide dismutase , 1999, Nature Structural Biology.

[117]  D. Borchelt,et al.  Protein Topology of Presenilin 1 , 1996, Neuron.

[118]  D. Borchelt,et al.  Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[119]  J. Buxbaum,et al.  Alzheimer Amyloid Protein Precursor in the Rat Hippocampus: Transport and Processing through the Perforant Path , 1998, The Journal of Neuroscience.

[120]  M. Frotscher,et al.  Cerebral Amyloid Induces Aberrant Axonal Sprouting and Ectopic Terminal Formation in Amyloid Precursor Protein Transgenic Mice , 1999, The Journal of Neuroscience.

[121]  S. W. Davies,et al.  Intranuclear Neuronal Inclusions in Huntington's Disease and Dentatorubral and Pallidoluysian Atrophy: Correlation between the Density of Inclusions andIT15CAG Triplet Repeat Length , 1998, Neurobiology of Disease.

[122]  J. Valentine,et al.  Delivering Copper Inside Yeast and Human Cells , 1997, Science.

[123]  John Q Trojanowski,et al.  Neurodegenerative Tauopathies Human Disease and Transgenic Mouse Models , 1999, Neuron.

[124]  D. Price,et al.  Motor neurone disease and animal models , 1994, Neurobiology of Disease.

[125]  Gurparkash Singh,et al.  Mutant Human Presenilin 1 Protects presenilin 1 Null Mouse against Embryonic Lethality and Elevates Aβ1–42/43 Expression , 1998, Neuron.

[126]  H. Zoghbi,et al.  Polyglutamine diseases: protein cleavage and aggregation , 1999, Current Opinion in Neurobiology.

[127]  R. Sherrington,et al.  Presenilin Proteins Undergo Heterogeneous Endoproteolysis between Thr291and Ala299and Occur as Stable N- and C-Terminal Fragments in Normal and Alzheimer Brain Tissue , 1997, Neurobiology of Disease.

[128]  T. Oltersdorf,et al.  Cleavage of amyloid beta peptide during constitutive processing of its precursor. , 1990, Science.

[129]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[130]  A Hofman,et al.  Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. , 1998, Human molecular genetics.

[131]  Q. Zhu,et al.  Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[132]  D. Selkoe,et al.  Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production , 1992, Nature.

[133]  M. Cudkowicz,et al.  Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene , 1998, Annals of neurology.

[134]  J. Roder,et al.  Inducible gene expression in the nervous system of transgenic mice. , 1998, Annual review of neuroscience.

[135]  B. Sommer,et al.  Neuron loss in APP transgenic mice , 1998, Nature.

[136]  J. Treanor,et al.  Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. , 1999, Science.

[137]  Robert H. Brown,et al.  Superoxide Dismutase Activity, Oxidative Damage, and Mitochondrial Energy Metabolism in Familial and Sporadic Amyotrophic Lateral Sclerosis , 1993, Journal of neurochemistry.

[138]  J. Morrison,et al.  Life and death of neurons in the aging brain. , 1997, Science.

[139]  B. Winblad,et al.  A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N–terminus of β–amyloid , 1992, Nature Genetics.

[140]  D. Pollen,et al.  Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease , 1995, Nature.

[141]  Shin Lin,et al.  Metal ion chaperone function of the soluble Cu(I) receptor Atx1. , 1997, Science.

[142]  M. Gurney,et al.  Age-Dependent Penetrance of Disease in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis , 1995, Molecular and Cellular Neuroscience.

[143]  A Hirano,et al.  Neuropathology of ALS , 1996, Neurology.

[144]  D. Borchelt,et al.  Superoxide Dismutase 1 Subunits with Mutations Linked to Familial Amyotrophic Lateral Sclerosis Do Not Affect Wild-type Subunit Function (*) , 1995, The Journal of Biological Chemistry.

[145]  G. V. Van Hoesen,et al.  The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. , 1991, Cerebral cortex.

[146]  M. Beal,et al.  Elevated “Hydroxyl Radical” Generation In Vivo in an Animal Model of Amyotrophic Lateral Sclerosis , 1998, Journal of neurochemistry.

[147]  Christina A. Wilson,et al.  Intracellular APP Processing and Aβ Production in Alzheimer Disease , 1999 .

[148]  D L Price,et al.  Alzheimer's disease: genetic studies and transgenic models. , 1998, Annual review of genetics.

[149]  S. W. Davies,et al.  Filamentous nerve cell inclusions in neurodegenerative diseases , 1998, Current Opinion in Neurobiology.

[150]  D. Borchelt,et al.  Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[151]  D. Price,et al.  Mutant genes in familial Alzheimer's disease and transgenic models. , 1998, Annual review of neuroscience.

[152]  L J Martin,et al.  Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. , 1999, Journal of neuropathology and experimental neurology.

[153]  W. Rosenblum The presence, origin, and significance of A beta peptide in the cell bodies of neurons. , 1999, Journal of neuropathology and experimental neurology.