title: Neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis, parkinsonism-dementia and neurologically normal Guamanians contain a 4- to 4.5-kilodalton protein which is immunoreactive to anti-amyloid beta/A4-protein antibodies.
abstract: Neurofibrillary tangles (NFT), one of the neurodegenerative features of Alzheimer's disease, Down's syndrome and normal aging, is a constant, widespread neuropathological finding in Guamanian amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD) and in neurologically normal Guamanians, dying of causes other than ALS and PD. NFT in brain tissue sections of patients with Guamanian ALS and PD were immunoreactive to antibodies directed against a 43-amino acid synthetic peptide homologous to amyloid beta/A4-protein (anti-SP43) associated with Alzheimer's disease. NFT extracted from frozen brain tissues of Guamanian patients with ALS and PD and from tissues of neurologically normal Guamanians were congophilic and birefringent. By negative-stain electron microscopy, NFT preparations contained bundles and/or isolated single, straight, unpaired filaments in Guamanian ALS and occasionally pairing of filaments in neurologically normal Guamanians, measuring 5-20 nm in diameter. Formic acid digestion of NFT preparations, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size-exclusion high-pressure liquid chromatography, showed a protein with an apparent molecular mass of 4- to 4.5-kDa, which by Western blot analysis was immunoreactive to anti-SP43. Immunoabsorption of purified NFT or SP43 with anti-SP43 abolished immunostaining. Our study corroborate previous data that amyloid beta/A4-protein is present in NFT in Guamanian PD. Furthermore, our data indicate that amyloid beta/A4-protein is present in NFT in brain tissues of patients with Guamanian ALS and in neurologically normal Guamanians, suggesting a common mechanism of amyloidogenesis with NFT formation in Alzheimer's disease and normal brain aging.
authors.affiliation: Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: D C
authors.initials: DC
authors.lastname: Guiroy
authors.forename: M
authors.initials: M
authors.lastname: Mellini
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: C
authors.initials: C
authors.lastname: Hilbich
authors.forename: J
authors.initials: J
authors.lastname: Safar
authors.forename: R M
authors.initials: RM
authors.lastname: Garruto
authors.forename: R
authors.initials: R
authors.lastname: Yanagihara
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: D C
authors.initials: DC
authors.lastname: Gajdusek
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003224:Congo Red; D003704:Dementia / Q000209:etiology / Q000473:pathology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006141:Guam; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000276:immunology / Q000473:pathology*; D010300:Parkinson Disease / Q000150:complications / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D003224:Congo Red