Search Results - (Author, Cooperation:J. Q. Trojanowski)

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  1. 1
    E. T. Cirulli ; B. N. Lasseigne ; S. Petrovski ; P. C. Sapp ; P. A. Dion ; C. S. Leblond ; J. Couthouis ; Y. F. Lu ; Q. Wang ; B. J. Krueger ; Z. Ren ; J. Keebler ; Y. Han ; S. E. Levy ; B. E. Boone ; J. R. Wimbish ; L. L. Waite ; A. L. Jones ; J. P. Carulli ; A. G. Day-Williams ; J. F. Staropoli ; W. W. Xin ; A. Chesi ; A. R. Raphael ; D. McKenna-Yasek ; J. Cady ; J. M. Vianney de Jong ; K. P. Kenna ; B. N. Smith ; S. Topp ; J. Miller ; A. Gkazi ; A. Al-Chalabi ; L. H. van den Berg ; J. Veldink ; V. Silani ; N. Ticozzi ; C. E. Shaw ; R. H. Baloh ; S. Appel ; E. Simpson ; C. Lagier-Tourenne ; S. M. Pulst ; S. Gibson ; J. Q. Trojanowski ; L. Elman ; L. McCluskey ; M. Grossman ; N. A. Shneider ; W. K. Chung ; J. M. Ravits ; J. D. Glass ; K. B. Sims ; V. M. Van Deerlin ; T. Maniatis ; S. D. Hayes ; A. Ordureau ; S. Swarup ; J. Landers ; F. Baas ; A. S. Allen ; R. S. Bedlack ; J. W. Harper ; A. D. Gitler ; G. A. Rouleau ; R. Brown ; M. B. Harms ; G. M. Cooper ; T. Harris ; R. M. Myers ; D. B. Goldstein
    American Association for the Advancement of Science (AAAS)
    Published 2015
    Staff View
    Publication Date:
    2015-02-24
    Publisher:
    American Association for the Advancement of Science (AAAS)
    Print ISSN:
    0036-8075
    Electronic ISSN:
    1095-9203
    Topics:
    Biology
    Chemistry and Pharmacology
    Computer Science
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*genetics ; Autophagy/*genetics ; Exome/*genetics ; Female ; Genes ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Protein Binding ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Risk ; Sequence Analysis, DNA ; Transcription Factor TFIIIA/genetics/metabolism ; Young Adult
    Published by:
    http://www.aaas.org/

    Latest Papers from Table of Contents or Articles in Press
  2. 2
    Staff View
    Publication Date:
    2013-03-05
    Publisher:
    Nature Publishing Group (NPG)
    Print ISSN:
    0028-0836
    Electronic ISSN:
    1476-4687
    Topics:
    Biology
    Chemistry and Pharmacology
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Amino Acid Sequence ; Amyotrophic Lateral Sclerosis/*genetics/metabolism/*pathology ; Animals ; Drosophila melanogaster/cytology/genetics/metabolism ; Female ; Frontotemporal Dementia/*genetics/metabolism/pathology ; HeLa Cells ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/*chemistry/genetics/*metabolism ; Humans ; Inclusion Bodies/genetics/metabolism/pathology ; Male ; Mice ; Molecular Sequence Data ; Muscular Dystrophies, Limb-Girdle/*genetics/metabolism/pathology ; Mutant Proteins/chemistry/*genetics/metabolism ; Mutation/*genetics ; Myositis, Inclusion Body/*genetics/metabolism/pathology ; Osteitis Deformans/*genetics/metabolism/pathology ; Peptide Termination Factors/chemistry/genetics/metabolism ; Prions/*chemistry/genetics/metabolism ; Protein Structure, Tertiary/genetics ; RNA/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism
    Published by:
    http://www.nature.com/

    Latest Papers from Table of Contents or Articles in Press
  3. 3
    K. C. Luk ; V. Kehm ; J. Carroll ; B. Zhang ; P. O'Brien ; J. Q. Trojanowski ; V. M. Lee
    American Association for the Advancement of Science (AAAS)
    Published 2012
    Staff View
    Publication Date:
    2012-11-20
    Publisher:
    American Association for the Advancement of Science (AAAS)
    Print ISSN:
    0036-8075
    Electronic ISSN:
    1095-9203
    Topics:
    Biology
    Chemistry and Pharmacology
    Computer Science
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Animals ; Cells, Cultured ; Corpus Striatum/drug effects/*metabolism/pathology ; Dopamine ; Dopaminergic Neurons/drug effects/metabolism/pathology ; Injections ; Lewy Bodies/drug effects/*metabolism/pathology ; Mice ; Parkinsonian Disorders/*metabolism/pathology ; Protein Folding ; Protein Transport ; Recombinant Proteins/administration & dosage/chemistry/metabolism ; Substantia Nigra/drug effects/metabolism/pathology ; alpha-Synuclein/administration & dosage/chemistry/*metabolism
    Published by:
    http://www.aaas.org/

    Latest Papers from Table of Contents or Articles in Press
  4. 4
    Staff View
    Publication Date:
    2018-09-04
    Publisher:
    Rockefeller University Press
    Print ISSN:
    0022-1007
    Electronic ISSN:
    1540-9538
    Topics:
    Medicine
    Keywords:
    Neuroscience
    Published by:
    http://www.rupress.org/

    Latest Papers from Table of Contents or Articles in Press
  5. 5
    HAROUSE, J. M. ; LAUGHLIN, M. ; HOXIE, J. A. ; TROJANOWSKI, J. Q. ; GONZALEZ-SCARANO, F.

    Oxford, UK : Blackwell Publishing Ltd
    Published 1989
    Staff View
    ISSN:
    1749-6632
    Source:
    Blackwell Publishing Journal Backfiles 1879-2005
    Topics:
    Natural Sciences in General
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1111/j.1749-6632.1989.tb16482.x

    Articles: DFG German National Licenses
  6. 6
    Schlaepfer, W. W. ; Lee, C. ; Trojanowski, J. Q. ; Lee, V. M.-Y.

    Oxford, UK : Blackwell Publishing Ltd
    Published 1984
    Staff View
    ISSN:
    1471-4159
    Source:
    Blackwell Publishing Journal Backfiles 1879-2005
    Topics:
    Medicine
    Notes:
    Abstract: Alterations occurring in nerve proteins of transected nerves were studied in rat sciatic nerves using polyclonal and monoclonal antibodies to identify and monitor neurofilament (NF) epitopes among nerve proteins following their electrophoresis and transfer to nitrocellulose paper. Immunoblot methods identified NF epitopes in NF triplet proteins (Mr 200,000, 150,000, and 68,000) and in NF nontriplet proteins (all other immunobands below Mr 200,000 and above Mr 40,000). NF triplet and nontriplet proteins were Triton-insoluble in both untransected and transected nerves. Extensive loss of NF triplet and most nontriplet proteins occurred during the 24-48-h period following nerve transection and was attributed to proteolytic degradation. Loss of protease-labile NF proteins led to a markedly reduced level of NF immunoreactivity in 2-day transected nerve. NF proteins which survived the 2-day posttransectional period were considered to represent protease-stable NF fragments. These fragments persisted in transected nerve for periods of at least 35 days. Most protease-stable NF fragments which retained immunoreactivity had Mr of 57,000-65,000. Low concentrations of the same immunobands were present in untransected nerves.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1111/j.1471-4159.1984.tb12809.x

    Articles: DFG German National Licenses
  7. 7
    Trojanowski, J. Q. ; Jacobson, S.
    Springer
    Published 1977
    Staff View
    ISSN:
    1432-1106
    Keywords:
    Cortico-pulvinar neurons ; Morphology ; Laminar distribution ; Monkey
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Using autoradiography and the horseradish peroxidase method, the morphology and laminar distribution of cortico-pulvinar neurons and the reciprocity of connections between pulvinar and cortex were examined in five Rhesus monkeys which had received medial, lateral and inferior pulvinar nucleus injections of both tritiated amino acids and horseradish peroxidase. Cortico-pulvinar neurons were identified in one heterotypical cortical area (area 17) and in many homotypical areas in frontal (areas 45, 46, 11, 12), parietal (5, 7), occipital (18, 19) and temporal (20, 21, 22) lobes. The cortico-pulvinar neurons were pyramidal in shape and ranged in size from small to large. In heterotypical cortex they were found in layers V and VI whereas in area 17 they were found only in layer Vb. Reciprocal connections between pulvinar and cortex were a feature of homotypical but not heterotypical cortex.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00237085

    Articles: DFG German National Licenses
  8. 8
    Staff View
    ISSN:
    1432-0533
    Keywords:
    High molecular weight neurofilament ; Phosphorylation ; Peripheral nervous system ; Amyotrophic lateral sclerosis ; Multiple system atrophy
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Using monoclonal antibody (Ta-51) that specifically binds phosphorylated high molecular weight neurofilament (pNFH) proteins, we investigated the occurrence of perikaryal pNFH in the spinal ventral horn motoneurons, intermediolateral column (ILC) neurons, sympathetic ganglion neurons and dorsal root ganglion (DRG) neurons obtained from patients with amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) and from control cases. In the controls, a system-dependent variation in perikaryal Ta-51 immunoreactivity was observed. Very few ventral horn cells and ILC neurons were stained with Ta-51, while large population of DRG neurons and sympathetic neurons were Ta-51 positive. The incidence of perikaryal immunoreactivity in the ventral horn cells was significantly increased in ALS and MSA. Some ILC neurons in ALS were Ta-51 positive and their incidence was significantly higher than that of the controls. These data suggest that both ILC neurons and ventral horn cells are affected with respect to pNFH metabolism in ALS and MSA. No significant difference was, however, detected in the Ta-51 immunoreactivity of both DRG and sympathetic ganglion neurons in ALS and MSA as compared with the controls.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00296785

    Articles: DFG German National Licenses
  9. 9
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Key words Apolipoprotein E ; Dementia ; Diffuse Lewy body disease ; Alzheimer's disease ; Parkinson's disease
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE ε4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE ε4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00296506

    Articles: DFG German National Licenses
  10. 10
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Key words Cholesterol metabolism ; Cytoskeleton ; Dementia
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Niemann-Pick Type C disease (NPC) is a cholesterol storage disease with defects in the intracellular trafficking of exogenous cholesterol derived from low density lipoproteins. In NPC cases with a chronic progressive course, neurofibrillary tangles (NFTs) that consist of paired helical filaments (PHFs) have been reported. To determine if NPC tangles contain abnormal tau proteins (known as PHFtau) similar to those found in Alzheimer's disease (AD) tangles, we examined the brains of five NPC cases by immunohistochemical and Western blot methods using a library of antibodies to defined epitopes of PHFtau. We show here that PHFtau in tangle-rich NPC brains is indistinguishable from PHFtau in AD brains. We speculate, that the generation of PHFtau in NPC may induce a cascade of pathological events that contribute to the widespread degeneration of neurons, and that these events may be similar in NPC and AD.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00318566

    Articles: DFG German National Licenses
  11. 11
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Key words Amyloid plaques ; Amyotrophic lateral ; sclerosis/parkinsonism-dementia complex ; Guam ; End-terminus-specific anti-amyloid β protein antibodies ; N-terminal modification of amyloid β protein
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract The Guamanian amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is characterized by abundant neurofibrillary pathology and neuron loss. In contrast to Alzheimer’s disease (AD), where extensive neurofibrillary lesions always occur with deposits of Aβ in numerous amyloid plaques, Aβ-rich amyloid plaques are absent or rare in most ALS/PDC patients. To characterize the amyloid plaques in the latter patients, we probed plaque-rich sections of their brains by immunohistochemistry using well-characterized antibodies to specific epitopes in the N and C termini of Aβ as well as to defined epitopes in hyperphosphorylated tau (PHFtau). The results indicate that the species of Aβ in the amyloid plaques of ALS/PDC patients resemble those detected in the amyloid plaques of cognitively intact subjects with pathological aging as well as patients with AD. However, the paucity of PHFtau-positive neurites in the ALS/PDC plaques suggests that they reflect pathological aging rather than AD.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s004010050774

    Articles: DFG German National Licenses
  12. 12
    Tremblay, G. F. ; Lee, V. M. -Y. ; Trojanowski, J. Q.
    Springer
    Published 1985
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Intermediate filaments ; Medulloblastoma ; Immunohistochemistry ; Immunoblotting
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Two methods of determining intermediate filament protein (IFP) expression by primitive brain tumors of childhood were compared using a panel of monoclonal antibodies to three classes of IFP. In addition to a controlled immunohistochemical study, a group of these tumors was subjected to direct immunologic assay of tumor-extracted IFP using the western blot method. Western blots of IFP extracted from ten prospectively microdissected brain tumors revealed no NF200 or NF150 in any tumor. Traces of NF68, VFP, and GFP were detected by this sensitive method in four, three, and six cases, respectively. Immunohistochemistry, using the same monoclonal antibodies on adjacent tumor sections, yielded results significantly different from the immunoblotting method: no NF proteins or VFP were detected, but immunoreactive GFP could be seen in a small percentage of cells in each case. A retrospective study of 46 primitive tumors, using only immunohistochemistry, showed GFP to be the most common source of immunopositivity (38 cases), followed by VFP (15 cases), but most positive cells were judged to be reactive astrocytes. NF protein was not detected except in three cases in which extremely rare cells had morphological features of neurons. Cells which were clearly malignant, and which constituted the majority of cells in a microscopic field, were devoid of any IFP immunoreactivity. The advantages and limitations of each method of IFP detection in this group of primitive tumors and the implications of the apparent paucity of mature neural IFP in these tumors are discussed.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00690201

    Articles: DFG German National Licenses
  13. 13
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Phosphorylated high molecular weight neurofilament ; Motor neuron ; Amyotrophic lateral sclerosis (ALS) ; Werdnig-Hoffmann's disease ; X-linked recessive bulbospinal neuronopathy
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00308716

    Articles: DFG German National Licenses
  14. 14
    Molenaar, W. M. ; Leij, L. ; Trojanowski, J. Q.
    Springer
    Published 1991
    Staff View
    ISSN:
    1432-0533
    Keywords:
    N-CAM ; Gliomas ; Neuroblastomas ; Neuroendocrine ; Primitive neuroectodermal tumors
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize “neural/neuroendocrine” or “neural” antigens, as defined by their reaction pattern in normal tissues and tumors. At least five of them recognize different epitopes of the neural cell adhesion molecule (N-CAM). It was found that all of 12 neuroblastomas, 2 ganglioneuroblastomas and 4 ganglioneuromas as well as 23 central primitive neuroectodermal tumors, 13 astrocytomas and 4 ependymomas share “neural/neuroendocrine” antigens (as defined by the anti-N-CAM antibodies Moc-1,-21,-32,-52 and-191) with SCLC. The “neural/neuroendocrine” antigen defined by Moc-171 was also found in all peripheral tumors, but only in further differentiated central tumors. Non-N-CAM related “neural” antigens (as defined by Moc-51 and-172) were found only in better-differentiated peripheral and central tumors, but they could be demonstrated in all three medulloblastoma cell lines studied. In addition, the antigen defined by Moc-51 was demonstrated in an immunoblot of a neuroblastoma cell line. Antibodies recognizing “epithelia” antigens of SCLC and other epithelia and their tumors (Moc-31 and-181) were non-reactive. It was concluded that these findings give further support for a relation between neural and neuroendocrine tumors and that some of the antibodies may be useful for the detection of differentiation in neural tumors. Antibodies with an “epithelia” recognition pattern may serve to distinguish neural from neuroendocrine tumors.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00294429

    Articles: DFG German National Licenses
  15. 15
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Key words: Diffuse Lewy Body Disease – Hippocampus – Neurites – Neurofilament – Ubiquitin
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract. Ubiquitin-immunoreactive dystrophic neurites in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease (DLBD). The origin of dystrophic CA2/3 neurites is unknown, but their extent correlates with the number of cortical Lewy bodies (LBs). To examine the molecular composition of these lesions, hippocampal sections were obtained at postmortem from cases of DLBD, Parkinson's disease and Alzheimer's disease. The tissue samples were fixed in a variety of fixatives and immunostained with antibodies to ubiquitin, ubiquitin C-terminal hydrolase (PGP9.5), neurofilament protein subunits, tau protein, paired helical filaments and tyrosine hydroxylase (TH). In addition to being ubiquitin positive, both cortical LBs and CA2/3 dystrophic neurites were positive with a neurofilament monoclonal antibody (RM032) and PGP9.5; however, fewer lesions were detected with these antibodies compared to ubiquitin immunocytochemistry. The dystrophic CA2/3 neurites were not stained with antibodies to tau proteins, paired helical filaments or TH. Absence of TH immunoreactivity suggests that CA2/3 neuritic processes are not derived from brain stem dopaminergic afferents to the hippocampus. Since CA2/3 neurites are immunologically similar to cortical LB, the pathogenesis of these lesions may be similar. Characterization of dystrophic CA2/3 neurites and cortical LBs may clarify how these lesions contribute to the emergence of dementia in DLBD.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00296742

    Articles: DFG German National Licenses
  16. 16
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Diffuse Lewy Body Disease ; Hippocampus ; Neurites ; Neurofilament ; Ubiquitin
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Ubiquitin-immunoreactive dystrophic neurites in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease (DLBD). The origin of dystrophic CA2/3 neurites is unknown, but their extent correlates with the number of cortical Lewy bodies (LBs). To examine the molecular composition of these lesions, hippocampal sections were obtained at postmortem from cases of DLBD, Parkinson's disease and Alzheimer's disease. The tissue samples were fixed in a variety of fixatives and immunostained with antibodies to ubiquitin, ubiquitin C-terminal hydrolase (PGP9.5), neurofilament protein subunits, tau protein, paired helical filaments and tyrosine hydroxylase (TH). In addition to being ubiquitin positive, both cortical LBs and CA2/3 dystrophic neurites were positive with a neurofilament monoclonal antibody (RM032) and PGP9.5; however, fewer lesions were detected with these antibodies compared to ubiquitin immunocyto-chemistry. The dystrophic CA2/3 neurites were not stained with antibodies to tau proteins, paired helical filaments or TH. Absence of TH immunoreactivity suggests that CA2/3 neuritic processes are not derived from brain stem dopaminergic afferents to the hippocampus. Since CA2/3 neurites are immunologically similar to cortical LB, the pathogenesis of these lesions may be similar. Characterization of dystrophic CA2/3 neurites and cortical LBs may clarify how these lesions contribute to the emergence of dementia in DLBD.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00296742

    Articles: DFG German National Licenses
  17. 17
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Apolipoprotein E ; Dementia ; Diffuse Lewy body disease ; Alzheimer's disease ; Parkinson's disease
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE ɛ4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE ɛ4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00296506

    Articles: DFG German National Licenses
  18. 18
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Key words Amyotrophy ; Axonopathy ; Neurofilaments ; Tau protein ; Transgenic mice
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Coding region and intronic mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17. Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats. Here we have expressed the longest four-repeat human brain tau isoform in transgenic mice under the control of the murine Thy1 promoter. Transgenic mice aged 3 weeks to 25 months overexpressed human tau protein in nerve cells of brain and spinal cord. Numerous abnormal, tau-immunoreactive nerve cell bodies and dendrites were seen. In addition, large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. When motor function was tested, transgenic mice showed signs of muscle weakness. Taken together, these findings demonstrate that overexpression of human four-repeat tau leads to a central and peripheral axonopathy that results in nerve cell dysfunction and amyotrophy.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s004010051148

    Articles: DFG German National Licenses
  19. 19
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Cholesterol metabolism ; Cytoskeleton ; Dementia
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Niemann-Pick Type C disease (NPC) is a cholesterol storage disease with defects in the intracellular trafficking of exogenous cholesterol derived from low density lipoproteins. In NPC cases with a chronic progressive course, neurofibrillary tangles (NFTs) that consist of paired helical filaments (PHFs) have been reported. To determine if NPC tangles contain abnormal tau proteins (known as PHFtau) similar to those found in Alzheimer's disease (AD) tangles, we examined the brains of five NPC cases by immunohistochemical and Western blot methods using a library of antibodies to defined epitopes of PHFtau. We show here that PHFtau in tangle-rich NPC brains is indistinguishable from PHFtau in AD brains. We speculate, that the generation of PHFtau in NPC may induce a cascade of pathological events that contribute to the widespread degeneration of neurons, and that these events may be similar in NPC and AD.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00318566

    Articles: DFG German National Licenses
  20. 20
    Arnold, S. E. ; Trojanowski, J. Q.
    Springer
    Published 1996
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Key words Neuropathology ; Schizophrenia ; Postmortem ; Neurodevelopment ; Neurdegenerative
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract The search for the defining neuropathology of schizophrenia continues to be one of the highest priority areas of research into this severely debilitating and common neuropsychiatric disorder. While lesions that are diagnostic of the disorder have not yet been identified, recent efforts employing molecule-specific probes and quantitative methods of analysis have enumerated many potentially important findings in the brains of patients with schizophrenia that warrant confirmation and elucidation. In this review, the major findings of six broad areas of neuropathological investigation are summarized and discussed. While substantial controversy exists in all areas, in sum: (1) diagnostic neuropathological investigations find only assorted and nonspecific abnormalities in the brains of schizophrenics that are likely to be representative of lesions found in age-compatible control groups; (2) morphometric studies of gross structures generally confirm the clinical in vivo neuroimaging findings of enlarged ventricles, decreased size of ventromedial temporal lobe structures, and decreased parahippocampal cortical thickness; (3) morphometric microscopy studies find frequent alterations in neuron density and decreased neuron size in limbic, temporal, and frontal regions; (4) investigations of connectivity are at an early stage but describe abnormal dendritic spine densities in the cortex, various changes in synaptic vesicle protein expression in limbic, temporal, and frontal cortices, and alterations in glutamatergic, catecholaminergic, and intrinsic innervation in anterior cingulate cortex – together, these findings suggest a “miswiring” in the schizophrenic brain; (5) investigations of aberrant neurodevelopment in schizophrenia describe abnormalities in cortical cytoarchitecture and several developmentally regulated proteins in the hippocampal region suggesting abnormal neuronal migration, differentiation, and/or cell pruning; and (6) studies of neurodegeneration and neural injury find a general lack of neurodegenerative disease lesions or ongoing astrocytosis that would indicate post-maturational neural injury.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s004010050512

    Articles: DFG German National Licenses