Cairns, Nigel J

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ALZHEIMER NEUROFIBRILLARY TANGLES--BIOCHEMICAL STUDIES

Iqbal, Khalid

1 September 1981 - 31 August 1985
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Total Funding: $ 171,179

The long term objective of this proposal is to learn the etiology and pathogenesis of neurofibrillary tangle of paired helical filaments (PHF) which is the most striking lesion in dementias of the Alzheimer type and in several conditions with mental retardation. The concentration of this lesion correlates directly to the degree of dementia. The studies proposed in this application are designed to determine the biochemical origin of the PHF. We have developed a method for isolation of highly purified preparations of PHF. We will purify PHF from autopsied Alzheimer brains to near homogeneity, identify its protein subunit/s, purifiy each of these proteins and in comparison with purified normal neurofibrous proteins characterize each PHF protein a) chemically by peptide maps, amino-terminal and carboxy-terminal analysis and amino acid composition, and b) immunochemically and immunocytochemically by Ouchterlony double diffusion test, immunobinding by 125I Protein A method on strips of polyacrylamide slab gels, and immunolabeling with and without immunoabsorption at light microscopic level by immunofluorescence and peroxidase-antiperoxidase (PAP) methods, and electron microscopic level by PAP and immunoperoxidase methods. We will also purify PHF from cases of Guam Parkinsonism dementia complex and Down syndrome (adult cases) and isolate PHF proteins and characterize these in comparison with PHF proteins from cases of Alzheimer disease, and study the immunocytochemical reaction of antisera to PHF proteins from Alzheimer brains with a) neurofibrillary changes of PHF in other human conditions such as normal aging, senile dementia, Guam Parkinsonism dementia, dementia pugilistica, Down syndrome, Hallerworden-Spatz disease and subacute sclerosing panencephalitis, b) neurofibrillary accumulation of 15 nm fibers in human diseases such as Steele-Richardson-Olszewski syndrome and c) neurofibrillary accumulation of 10 nm filaments in human disorders such as sporadic motor neuron disease, vincristine neuropathy and infantile neuroaxonal dystrophy, and in experimental animal conditions such as colchicine-induced neurofibrillary changes in rabbits.

14 Resulting Publications

• 1.

  1987

  K Iqbal; I Grundke-Iqbal; P A Merz; H M Wisniewski; T Zaidi

  In vitro assembly and isolation of neurofilaments and microtubules from mammalian CNS.

  Brain research 1987;388(2):163-72.

• 2.

  1987

  I Alafuzoff; R Adolfsson; I Grundke-Iqbal; B Winblad

  Blood-brain barrier in Alzheimer dementia and in non-demented elderly. An immunocytochemical study.

  Acta neuropathologica 1987;73(2):160-6.

• 3.

  1987

  H M Wisniewski; K Iqbal; I Grundke-Iqbal; R Rubenstein

  The solubility controversy of paired helical filaments: a commentary.

  Neurochemical research 1987;12(1):93-5.

• 4.

  1987

  I Alafuzoff; K Iqbal; H Friden; R Adolfsson; B Winblad

  Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis.

  Acta neuropathologica 1987;74(3):209-25.

• 5.

  1986

  K Iqbal; I Grundke-Iqbal; T Zaidi; P A Merz; G Y Wen; S S Shaikh; H M Wisniewski; I Alafuzoff; B Winblad

  Defective brain microtubule assembly in Alzheimer's disease.

  Lancet 1986;2(8504):421-6.

• 6.

  1986

  K Iqbal; I Grundke-Iqbal; T Zaidi; N Ali; H M Wisniewski

  Are Alzheimer neurofibrillary tangles insoluble polymers?

  Life sciences 1986;38(18):1695-700.

• 7.

  1986

  K Iqbal; I Grundke-Iqbal; H M Wisniewski

  Neuronal cytoskeleton in aging and dementia.

  Progress in brain research 1986;70():279-88.

• 8.

  1985

  K Iqbal; R A Somerville; C H Thompson; H M Wisniewski

  Brain glutamate decarboxylase and cholinergic enzyme activities in scrapie.

  Journal of the neurological sciences 1985;67(3):345-50.

• 9.

  1985

  I Grundke-Iqbal; G P Wang; K Iqbal; Y C Tung; H M Wisniewski

  Alzheimer paired helical filaments: identification of polypeptides with monoclonal antibodies.

  Acta neuropathologica 1985;68(4):279-83.

• 10.

  1985

  I Grundke-Iqbal; K Iqbal; Y C Tung; G P Wang; H M Wisniewski

  Alzheimer paired helical filaments: cross-reacting polypeptide/s normally present in brain.

  Acta neuropathologica 1985;66(1):52-61.

• 11.

  1984

  H M Wisniewski; P A Merz; K Iqbal

  Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle.

  Journal of neuropathology and experimental neurology 1984;43(6):643-56.

• 12.

  1984

  I Grundke-Iqbal; K Iqbal; Y C Tung; H M Wisniewski

  Alzheimer paired helical filaments: immunochemical identification of polypeptides.

  Acta neuropathologica 1984;62(4):259-67.

• 13.

  1984

  K Iqbal; T Zaidi; C H Thompson; P A Merz; H M Wisniewski

  Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition.

  Acta neuropathologica 1984;62(3):167-77.

• 14.

  1984

  G P Wang; I Grundke-Iqbal; R J Kascsak; K Iqbal; H M Wisniewski

  Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s).

  Acta neuropathologica 1984;62(4):268-75.

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