The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products

Bibliographic Details
Main Author:	Palmert, Mark Raney
Language:	English
Published:	Case Western Reserve University School of Graduate Studies / OhioLINK 1990
Subjects:	beta amyloid protein precursor Alzheimer's disease mRNAs protein products
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=case1054920188

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-case10549201882021-08-03T05:30:26Z The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products Palmert, Mark Raney beta amyloid protein precursor Alzheimer's disease mRNAs protein products The amyloid deposited in Alzheimer's disease (AD) is composed primarily of a 4.2 kDa protein (the β amyloid protein, βAP) that is derived from a larger β amyloid protein precursor. This thesis confirms the identification of four ∼110-135 kDa membrane-associated proteins in human brain as the full-length forms of the βAPP and demonstrates that only the two largest contain the alternatively spliced Kunitz protease inhibitor (KPI) domain. Three soluble, amino-terminal derivatives of the βAPP are also identified: ∼125 kDa KPI-containing and ∼105 and ∼25 kDa KPI-free proteins. These proteins are present in human brain and cerebrospinal fluid (CSF), lack the carboxyl terminus of the full-length forms, and have amino-terminal sequences that prove they are βAPP derivatives. Both the ∼125 and ∼105 kDa derivatives contain at least part of the βAP because both are specifically labeled by anti-βAP antibodies. Thus, subtle changes in the production or processing of soluble βAPP derivatives could drive βAP generation and amyloid deposition. These changes could be due to direct alterations in βAPP processing, to indirect changes caused by altered βAPP gene expression, or to a combination of the two . These possibilities are addressed by using in situ hybridization to examine βAPP gene expression and by quantitating the three soluble derivatives in CSF to assess βAPP processing. In AD, significant increases in βAPP mRNA lacking the KPI domain are observed in two subcortical nuclei that project diffusely to the cerebral cortex, degenerate in AD, and have axons that are found in senile plaques. This result suggests that increased amounts of KPI-free βAPP mRNA may play a role in accelerating the rate at which the βAP is formed in AD. In the CSF samples, significant changes in the relative and absolute amounts of the three derivatives are identified that occur in normal aging, to a greater extent in AD, and that correlate with the mental status of the AD patients. Thus, it appears that both βAPP gene expression and posttranslational processing are altered in AD. Moreover, these alterations may reflect fundamental mechanisms responsible for amyloid deposition. 1990 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1054920188 http://rave.ohiolink.edu/etdc/view?acc_num=case1054920188 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	beta amyloid protein precursor Alzheimer's disease mRNAs protein products
spellingShingle	beta amyloid protein precursor Alzheimer's disease mRNAs protein products Palmert, Mark Raney The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products
author	Palmert, Mark Raney
author_facet	Palmert, Mark Raney
author_sort	Palmert, Mark Raney
title	The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products
title_short	The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products
title_full	The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products
title_fullStr	The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products
title_full_unstemmed	The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products
title_sort	beta amyloid protein precursor of alzheimer's disease: analysis of mrnas and protein products
publisher	Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate	1990
url	http://rave.ohiolink.edu/etdc/view?acc_num=case1054920188
work_keys_str_mv	AT palmertmarkraney thebetaamyloidproteinprecursorofalzheimersdiseaseanalysisofmrnasandproteinproducts AT palmertmarkraney betaamyloidproteinprecursorofalzheimersdiseaseanalysisofmrnasandproteinproducts
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The beta amyloid protein precursor of Alzheimer's disease: Analysis of mRNAs and protein products

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