Alzheimer's disease amyloid precursor protein is present in senile plaques and cerebrospinal fluid: Immunohistochemical and biochemical characterization

1989 ◽  
Vol 163 (1) ◽  
pp. 430-437 ◽  
Author(s):  
Jorge Ghiso ◽  
Fabrizio Tagliavini ◽  
Willem Frederik Timmers ◽  
Blas Frangione
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Precursor Protein ◽  
Biochemical Characterization ◽  
Senile Plaques ◽  
Precursor Protein

Levels of α- and β-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients

2000 ◽  
Vol 278 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Kristina Sennvik ◽  
Johan Fastbom ◽  
Mari Blomberg ◽  
Lars-Olof Wahlund ◽  
Bengt Winblad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Precursor Protein ◽  
Precursor Protein

Protein–protein interactions in the assembly and subcellular trafficking of the BACE (β-site amyloid precursor protein-cleaving enzyme) complex of Alzheimer's disease

2007 ◽  
Vol 35 (5) ◽  
pp. 974-979 ◽  
Author(s):  
R.B. Parsons ◽  
B.M. Austen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Protein Interactions ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid ◽  
Ad Alzheimer’S Disease

The correct assembly of the BACE (β-site amyloid precursor protein-cleaving enzyme or β-secretase) complex and its subsequent trafficking to cellular compartments where it associates with the APP (amyloid precursor protein) is essential for the production of Aβ (amyloid β-peptide), the protein whose aggregation into senile plaques is thought to be responsible for the pathogenesis of AD (Alzheimer's disease). These processes rely upon both transient and permanent BACE–protein interactions. This review will discuss what is currently known about these BACE–protein interactions and how they may reveal novel therapeutic targets for the treatment of AD.

scholarly journals The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

2012 ◽  
Vol 11 (11) ◽  
pp. 1274-1288 ◽  
Author(s):  
Andreas Schrötter ◽  
Kathy Pfeiffer ◽  
Fouzi El Magraoui ◽  
Harald W. Platta ◽  
Ralf Erdmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Senile Plaques ◽  
Mrna Level ◽  
Family Members ◽  
Precursor Protein ◽  
A Cell ◽  
Psen1 Gene

Central hallmark of Alzheimer's disease are senile plaques mainly composed of β-amyloid, which is a cleavage product of the amyloid precursor protein (APP). The physiological function of APP and its family members APLP1 and APLP2 is poorly understood. In order to fill this gap, we established a cell-culture based model with simultaneous knockdown of all members of the family. A comprehensive proteome study of the APP/APLP1/APLP2 knockdown cell lysates versus controls revealed significant protein abundance changes of more than 30 proteins. Targeted validation of selected candidates by immunoblotting supported the significant down-regulation of the methionine adenosyltransferase II, alpha (MAT2A) as well as of peroxiredoxin 4 in the knockdown cells. Moreover, MAT2A was significantly down-regulated at the mRNA level as well. MAT2A catalyzes the production of S-adenosylmethionine from methionine and ATP, which plays a pivotal role in the methylation of neurotransmitters, DNA, proteins, and lipids. MAT2A-dependent significant up-regulation of S-adenosylmethionine was also detectable in the knockdown cells compared with controls. Our results point to a role of the APP family proteins in cellular methylation mechanisms and fit to findings of disturbed S-adenosylmethionine levels in tissue and CSF of Alzheimer disease patients versus controls. Importantly, methylation plays a central role for neurotransmitter generation like acetylcholine pointing to a crucial relevance of our findings for Alzheimer's disease. In addition, we identified differential gene expression of BACE1 and PSEN1 in the knockdown cells, which is possibly a consequence of MAT2A deregulation and may indicate a self regulatory mechanism.

scholarly journals Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to AβPeptide-Induced Membrane Changes

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Sholpan Askarova ◽  
Xiaoguang Yang ◽  
James C.-M. Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Conformational Changes ◽  
Senile Plaques ◽  
Critical Role ◽  
Protein A ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Membrane Composition

An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-βpeptide (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD), are strongly associated with its ability to interact with membranes of neurons and other cerebral cells. Aβis derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) byβ- andγ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved byα-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP,α-,β-, andγ-secretases are membrane-associated proteins, AβPP processing and Aβproduction can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβcytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding the mechanisms leading to changes in a membrane's biophysical properties and how they affect AβPP processing and Aβtoxicity should prove to provide new therapeutic strategies for prevention and treatment of AD.

scholarly journals Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Drosophila Models of Alzheimer’s Disease

2021 ◽  
Vol 22 (13) ◽  
pp. 7022
Author(s):  
David Jalali ◽  
Justine Anne Guevarra ◽  
Luz Martinez ◽  
Lily Hung ◽  
Fernando J Vonhoff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Amyloid Precursor Protein ◽  
Senile Plaques ◽  
Precursor Protein ◽  
Mammalian Brain ◽  
Shed Light ◽  
Drosophila Models

Studies using animal models have shed light into the molecular and cellular basis for the neuropathology observed in patients with Alzheimer’s disease (AD). In particular, the role of the amyloid precursor protein (APP) plays a crucial role in the formation of senile plaques and aging-dependent degeneration. Here, we focus our review on recent findings using the Drosophila AD model to expand our understanding of APP molecular function and interactions, including insights gained from the fly homolog APP-like (APPL). Finally, as there is still no cure for AD, we review some approaches that have shown promising results in ameliorating AD-associated phenotypes, with special attention on the use of nutraceuticals and their molecular effects, as well as interactions with the gut microbiome. Overall, the phenomena described here are of fundamental significance for understanding network development and degeneration. Given the highly conserved nature of fundamental signaling pathways, the insight gained from animal models such as Drosophila melanogaster will likely advance the understanding of the mammalian brain, and thus be relevant to human health.

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