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Molecular pathology of Alzheimer neurofibrillary degeneration.
Acta Neurobiol Exp (Wars). 1993; 53(1):325-35.AN

Abstract

The most characteristic brain lesion of Alzheimer disease is the accumulation of paired helical filaments (PHF) in the affected neurons. Based on solubility in detergents there are two general populations of PHF, the readily soluble (PHF I) and the sparingly soluble (PHF II) types. The major polypeptides of PHF are the microtubule associated protein tau. Tau in PHF is present in abnormally phosphorylated forms. In addition to the PHF, the abnormal tau is also present in unpolymerized form in the AD brain. Small amounts of ubiquitin (%) are associated with PHF II but neither with PHF I nor with the unpolymerized abnormally phosphorylated tau in AD brain. Furthermore, the pretangle neurons can readily be immunolabeled for abnormally phosphorylated tau but not for ubiquitin. The level of tau in neocortex is several-fold higher than in AD aged control cases, but this increase is in the form of the abnormally phosphorylated protein. The microtubule associated proteins from AD brain do not promote the assembly of microtubules in vitro, whereas the in vitro dephosphorylated PHF polypeptides stimulate the binding of GTP to the exchangeable site of tubulin and the assembly of microtubules. In vitro the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. It is suggested that a defect in the protein phosphorylation/dephosphorylation system leads to hyperphosphory-lation of tau. The altered tau contributes to a microtubule assembly defect and consequently compromises the axoplasmic flow and leads to neuronal degeneration.

Authors+Show Affiliations

New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

8317268

Citation

Iqbal, K, et al. "Molecular Pathology of Alzheimer Neurofibrillary Degeneration." Acta Neurobiologiae Experimentalis, vol. 53, no. 1, 1993, pp. 325-35.
Iqbal K, Alonso A, Gong C, et al. Molecular pathology of Alzheimer neurofibrillary degeneration. Acta Neurobiol Exp (Wars). 1993;53(1):325-35.
Iqbal, K., Alonso, A., Gong, C., Khatoon, S., Kudo, T., Singh, T., & Grundke-Iqbal, I. (1993). Molecular pathology of Alzheimer neurofibrillary degeneration. Acta Neurobiologiae Experimentalis, 53(1), 325-35.
Iqbal K, et al. Molecular Pathology of Alzheimer Neurofibrillary Degeneration. Acta Neurobiol Exp (Wars). 1993;53(1):325-35. PubMed PMID: 8317268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular pathology of Alzheimer neurofibrillary degeneration. AU - Iqbal,K, AU - Alonso,A, AU - Gong,C, AU - Khatoon,S, AU - Kudo,T, AU - Singh,T, AU - Grundke-Iqbal,I, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 325 EP - 35 JF - Acta neurobiologiae experimentalis JO - Acta Neurobiol Exp (Wars) VL - 53 IS - 1 N2 - The most characteristic brain lesion of Alzheimer disease is the accumulation of paired helical filaments (PHF) in the affected neurons. Based on solubility in detergents there are two general populations of PHF, the readily soluble (PHF I) and the sparingly soluble (PHF II) types. The major polypeptides of PHF are the microtubule associated protein tau. Tau in PHF is present in abnormally phosphorylated forms. In addition to the PHF, the abnormal tau is also present in unpolymerized form in the AD brain. Small amounts of ubiquitin (%) are associated with PHF II but neither with PHF I nor with the unpolymerized abnormally phosphorylated tau in AD brain. Furthermore, the pretangle neurons can readily be immunolabeled for abnormally phosphorylated tau but not for ubiquitin. The level of tau in neocortex is several-fold higher than in AD aged control cases, but this increase is in the form of the abnormally phosphorylated protein. The microtubule associated proteins from AD brain do not promote the assembly of microtubules in vitro, whereas the in vitro dephosphorylated PHF polypeptides stimulate the binding of GTP to the exchangeable site of tubulin and the assembly of microtubules. In vitro the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. It is suggested that a defect in the protein phosphorylation/dephosphorylation system leads to hyperphosphory-lation of tau. The altered tau contributes to a microtubule assembly defect and consequently compromises the axoplasmic flow and leads to neuronal degeneration. SN - 0065-1400 UR - https://www.unboundmedicine.com/medline/citation/8317268/Molecular_pathology_of_Alzheimer_neurofibrillary_degeneration_ L2 - http://www.ane.pl/linkout.php?vol=53&no=1&fpp=325 DB - PRIME DP - Unbound Medicine ER -