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Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex.
J Neuropathol Exp Neurol. 1996 Oct; 55(10):1051-9.JN

Abstract

Guam Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (Guam ALS/PDC) is a progressive neurodegenerative disorder characterized by abundant neurofibrillary tangles (NFTs) composed of aggregated paired helical filaments (PHFs). These abnormal filaments resemble the PHFs in neurofibrillary lesions of classic Alzheimer's disease (AD), and recent studies demonstrated that tau in Guam ALS/PDC is aberrantly phosphorylated and biochemically similar to the abnormal tau proteins (PHFtau) in classic AD. However, unlike PHFtau in AD, there is little information on the specific sites of phosphorylation in PHFtau from Guam ALS/PDC. Thus, to address this important issue, we examined tangle-rich Guam ALS/PDC and AD brains by Western blot, immunoelectron microscopy and immunohistochemistry using 13 antibodies to defined phosphate-dependent or -independent epitopes distributed throughout AD PHFtau. These studies identified 7 previously unknown sites of phosphorylation in PHFtau from Guam ALS/PDC (i.e. Thr181, Thr231, Ser262, Ser396, Ser404, Ser422, and the site defined by monoclonal antibody AT10), all of which also are found in AD PHFtau. Indeed, the Western blot, light and immunoelectron microscopic data suggest that NFTs, PHFs and PHFtau in Guam ALS/PDC are very similar to their counterparts in classic AD. Thus, insights into mechanisms leading to the accumulation of neurofibrillary lesions in Guam ALS/PDC may advance understanding of the pathogenesis and biological consequences of these lesions in classic AD.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8858002

Citation

Mawal-Dewan, M, et al. "Identification of Phosphorylation Sites in PHF-TAU From Patients With Guam Amyotrophic Lateral Sclerosis/parkinsonism-dementia Complex." Journal of Neuropathology and Experimental Neurology, vol. 55, no. 10, 1996, pp. 1051-9.
Mawal-Dewan M, Schmidt ML, Balin B, et al. Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex. J Neuropathol Exp Neurol. 1996;55(10):1051-9.
Mawal-Dewan, M., Schmidt, M. L., Balin, B., Perl, D. P., Lee, V. M., & Trojanowski, J. Q. (1996). Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex. Journal of Neuropathology and Experimental Neurology, 55(10), 1051-9.
Mawal-Dewan M, et al. Identification of Phosphorylation Sites in PHF-TAU From Patients With Guam Amyotrophic Lateral Sclerosis/parkinsonism-dementia Complex. J Neuropathol Exp Neurol. 1996;55(10):1051-9. PubMed PMID: 8858002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex. AU - Mawal-Dewan,M, AU - Schmidt,M L, AU - Balin,B, AU - Perl,D P, AU - Lee,V M, AU - Trojanowski,J Q, PY - 1996/10/1/pubmed PY - 1996/10/1/medline PY - 1996/10/1/entrez SP - 1051 EP - 9 JF - Journal of neuropathology and experimental neurology JO - J Neuropathol Exp Neurol VL - 55 IS - 10 N2 - Guam Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (Guam ALS/PDC) is a progressive neurodegenerative disorder characterized by abundant neurofibrillary tangles (NFTs) composed of aggregated paired helical filaments (PHFs). These abnormal filaments resemble the PHFs in neurofibrillary lesions of classic Alzheimer's disease (AD), and recent studies demonstrated that tau in Guam ALS/PDC is aberrantly phosphorylated and biochemically similar to the abnormal tau proteins (PHFtau) in classic AD. However, unlike PHFtau in AD, there is little information on the specific sites of phosphorylation in PHFtau from Guam ALS/PDC. Thus, to address this important issue, we examined tangle-rich Guam ALS/PDC and AD brains by Western blot, immunoelectron microscopy and immunohistochemistry using 13 antibodies to defined phosphate-dependent or -independent epitopes distributed throughout AD PHFtau. These studies identified 7 previously unknown sites of phosphorylation in PHFtau from Guam ALS/PDC (i.e. Thr181, Thr231, Ser262, Ser396, Ser404, Ser422, and the site defined by monoclonal antibody AT10), all of which also are found in AD PHFtau. Indeed, the Western blot, light and immunoelectron microscopic data suggest that NFTs, PHFs and PHFtau in Guam ALS/PDC are very similar to their counterparts in classic AD. Thus, insights into mechanisms leading to the accumulation of neurofibrillary lesions in Guam ALS/PDC may advance understanding of the pathogenesis and biological consequences of these lesions in classic AD. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/8858002/Identification_of_phosphorylation_sites_in_PHF_TAU_from_patients_with_Guam_amyotrophic_lateral_sclerosis/parkinsonism_dementia_complex_ L2 - https://www.diseaseinfosearch.org/result/400 DB - PRIME DP - Unbound Medicine ER -