title: Altered amyloid beta-protein precursor processing in brains of patients with neuronal ceroid lipofuscinosis.
abstract: Our previous study disclosed strong immunostaining of brain tissue in neuronal ceroid lipofuscinosis (NCL) with antibodies against amyloid beta-protein and the presence of 31-kDa polypeptide in the storage material. In the present study, we investigated the immunoreactivity of the NCL brain tissue with anti-serum (anti-GID) raised against a synthetic peptide, based on the amyloid beta-protein precursor, with the 175-186 amino acid sequence. Immunocytochemistry was performed on autopsy brain material collected from 15 NCL cases, and from 8 age-matched normal controls. The results showed strong immunoreactivity of nerve cells in the NCL cases, which according to densitometry was 5 times more intense than in the control group (P less than 0.0001 by Student's t-test). Western blot analysis revealed that in protein fractions of NCL brain homogenates anti-GID recognized the protein band of 35 kDa. Thus our present and previously performed studies supplied for the first time data pointing to abnormal processing of amyloid beta-protein precursor in NCL. Moreover, the accumulation of both 31- and 35-kDa polypeptides that was demonstrated provides further support for postulated defective protein metabolism in this disorder.
authors: New York State Office of Mental Retardation and Developmental Disabilities, Department of Pathological Neurobiology, Staten Island 10314.
authors: K E
authors: KE
authors: Wisniewski
authors: E
authors: E
authors: Kida
authors: W
authors: W
authors: Gordon-Majszak
authors: T
authors: T
authors: Saitoh
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor; D001344:Autopsy; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011480:Protease Inhibitors / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011480:Protease Inhibitors; D011498:Protein Precursors