O1-06-06: Improved memory capacity of amyloid precursor protein transgenic mice through passive administration of a monoclonal antibody inducing a conformational shift of amyloid-beta

2006 ◽  
Vol 2 ◽  
pp. S21-S21
Author(s):  
Andreas Muhs ◽  
Sophie Lohmann ◽  
David Hickman ◽  
Maria Pihlgren ◽  
Luitgard Nagel-Steger ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Memory Capacity ◽  
Precursor Protein

scholarly journals Beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1)-mediated changes of endogenous amyloid beta in wild-type and transgenic mice in vivo

2008 ◽  
Vol 435 (3) ◽  
pp. 186-189 ◽  
Author(s):  
Chiho Hirata-Fukae ◽  
Elkhansa Hassan Sidahmed ◽  
Thomas P. Gooskens ◽  
Paul S. Aisen ◽  
Ilse Dewachter ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Wild Type

Trafficking of cell-surface amyloid beta-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody

1996 ◽  
Vol 109 (5) ◽  
pp. 991-998 ◽  
Author(s):  
E.H. Koo ◽  
S.L. Squazzo ◽  
D.J. Selkoe ◽  
C.H. Koo
Keyword(s):  
Monoclonal Antibody ◽  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Senile Plaques ◽  
Beta Amyloid ◽  
Precursor Protein ◽  
Secretory Product ◽  
Amyloid Beta Protein ◽  
Lysosomal Compartment

Amyloid beta-protein, the principal constituent of amyloid fibrils found in senile plaques and blood vessels in Alzheimer's disease, is constitutively produced and released into medium of cultured cells. Amyloid beta-protein is derived by proteolysis of the beta-amyloid precursor protein by unclear mechanisms. Beta-amyloid precursor protein is a transmembrane protein which can be processed to release a large secretory product or processed in the endosomal/lysosomal pathway without secretion. Previous studies have shown that from the cell surface, beta-amyloid precursor protein may be released after cleavage or internalized without cleavage, the latter in a pathway that both produces amyloid beta-protein and also targets some molecules to the lysosomal compartment. Analysis of beta-amyloid precursor protein trafficking is confounded by the concomitant secretion and internalization of molecules from the cell surface. To address this issue, we developed an assay, based on the binding of radioiodinated monoclonal antibody, to measure the release and internalization of cell surface beta-amyloid precursor protein in transfected cells. With this approach, we showed that surface beta-amyloid precursor protein is either rapidly released or internalized, such that the duration at the cell surface is very short. Approximately 30% of cell surface beta-amyloid precursor protein molecules are released. Following internalization, a fraction of molecules are recycled while the majority of molecules are rapidly sorted to the lysosomal compartment for degradation When the C terminus of beta-amyloid precursor protein is deleted, secretion is increased by approximately 2.5-fold as compared to wild-type molecules. There is concomitant decrease in internalization in these mutant molecules as well as prolongation of the resident time on the cell surface. This observation is consistent with recent evidence that signals within the cytoplasmic domain mediate beta-amyloid precursor protein internalization.

Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice

2016 ◽  
Vol 478 (1) ◽  
pp. 286-292 ◽  
Author(s):  
Sun Ah Park ◽  
Nathalie Chevallier ◽  
Karishma Tejwani ◽  
Mary M. Hung ◽  
Hiroko Maruyama ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Amyloid Beta Protein ◽  
Cox 2 ◽  
Cox 1

G-lymphatic, vascular and immune pathways for Aβ clearance cascade and therapeutic targets for Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurav Chakraborty ◽  
Jyothsna ThimmaReddygari ◽  
Divakar Selvaraj
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Complement System ◽  
Therapeutic Targets ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Beta Peptide ◽  
Immune Pathways

The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of accumulation of extracellular amyloid beta peptides. Here, the clearance of amyloid beta peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines and the complement system also have a major role in Alzheimer disease. The physiological clearance pathways involved in amyloid beta peptide are glymphatic, vascular and immune pathways. Amyloid precursor protein, low density lipoprotein receptor-related protein 1, receptor for advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines and microglia are involved in amyloid beta peptide clearance pathways across the blood brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid beta agglomeration. This insoluble amyloid beta leads to neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

scholarly journals Remodeling Alzheimer-amyloidosis models by seeding

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Brittany S. Ulm ◽  
David R. Borchelt ◽  
Brenda D. Moore
Keyword(s):  
Amyloid Precursor Protein ◽  
Neurodegenerative Diseases ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Time Interval ◽  
Murine Models ◽  
Brain Pathology ◽  
Amyloid Deposits ◽  
Transgenic Murine Models ◽  
Mutant Genes

AbstractAlzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.

Changes in Amyloid-  and Tau in the Cerebrospinal Fluid of Transgenic Mice Overexpressing Amyloid Precursor Protein

2013 ◽  
Vol 5 (194) ◽  
pp. 194re2-194re2 ◽  
Author(s):  
L. F. Maia ◽  
S. A. Kaeser ◽  
J. Reichwald ◽  
M. Hruscha ◽  
P. Martus ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Precursor Protein
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