β-Amyloid precursor protein staining of the brain in sudden infant and early childhood death

2014 ◽  
Vol 40 (4) ◽  
pp. 385-397 ◽  
Author(s):  
Lisbeth Lund Jensen ◽  
Jytte Banner ◽  
Benedicte Parm Ulhøi ◽  
Roger W Byard
Keyword(s):  
Early Childhood ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Sudden Infant ◽  
Childhood Death ◽  
Β Amyloid ◽  
Protein Staining ◽  
The Brain

scholarly journals Transmissible Endosomal Intoxication: A Balance between Exosomes and Lysosomes at the Basis of Intercellular Amyloid Propagation

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 272
Author(s):  
Anaïs Bécot ◽  
Charlotte Volgers ◽  
Guillaume van Niel
Keyword(s):  
Amyloid Precursor Protein ◽  
Neurodegenerative Diseases ◽  
Multivesicular Body ◽  
Precursor Protein ◽  
Aβ Peptides ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Novel Concept ◽  
The Brain

In Alzheimer′s disease (AD), endolysosomal dysfunctions are amongst the earliest cellular features to appear. Each organelle of the endolysosomal system, from the multivesicular body (MVB) to the lysosome, contributes to the homeostasis of amyloid precursor protein (APP) cleavage products including β-amyloid (Aβ) peptides. Hence, this review will attempt to disentangle how changes in the endolysosomal system cumulate to the generation of toxic amyloid species and hamper their degradation. We highlight that the formation of MVBs and the generation of amyloid species are closely linked and describe how the molecular machineries acting at MVBs determine the generation and sorting of APP cleavage products towards their degradation or release in association with exosomes. In particular, we will focus on AD-related distortions of the endolysomal system that divert it from its degradative function to favour the release of exosomes and associated amyloid species. We propose here that such an imbalance transposed at the brain scale poses a novel concept of transmissible endosomal intoxication (TEI). This TEI would initiate a self-perpetuating transmission of endosomal dysfunction between cells that would support the propagation of amyloid species in neurodegenerative diseases.

scholarly journals The effect of cannabinoids on APP, BACE1, and ApoE mRNA expression

SURG Journal ◽  
2014 ◽  
Vol 7 (1) ◽  
pp. 47-55
Author(s):  
Navjit Brar
Keyword(s):  
Amyloid Precursor Protein ◽  
Apolipoprotein E ◽  
Mrna Expression ◽  
Cell Line ◽  
Cb1 Receptor ◽  
Precursor Protein ◽  
Mrna Levels ◽  
Β Amyloid ◽  
Apoe Mrna ◽  
The Brain

Alzheimer's disease (AD) is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmark of this disease is the deposition of β-amyloid protein plaques (Aβ) in the brain, which evoke neuronal cell death and impair inter-neuronal communication. Past studies have suggested that cannabinoids reduce the levels of Aβ in the brain; however, little is known about the mechanisms involved in this process. In this study, the SH-SY5Y cell line was first examined for expression of amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), and apolipoprotein E (ApoE), genes involved in Aβ production and clearance. All three genes were expressed and detected in the cell line. We then observed the effects of the endocannabinoid anandamide, a CB1 receptor agonist, on the mRNA expression of APP, BACE1, and ApoE in SH-SY5Y cells. After 48h exposure to anandamide, mRNA levels of APP and BACE1 significantly decreased, which could contribute to reduced Aβ levels. The mechanism of action by which anandamide reduces mRNA levels of APP and BACE1 should be further investigated. ApoE mRNA levels were not found to be significantly changed, suggesting that anandamide does not affect mRNA expression of this gene. The effects of cannabinoids on ApoE levels should be further studied as the effects may occur at a level different from mRNA expression and may even occur via a pathway unrelated to CB1 receptor activation. Keywords: Alzheimer’s disease; β-amyloid; anandamide; amyloid precursor protein; beta-site APP cleaving enzyme 1; apolipoprotein E

Methotrexate-Related Nonnecrotizing Multifocal Axonopathy Detected by β-Amyloid Precursor Protein Immunohistochemistry

2002 ◽  
Vol 126 (1) ◽  
pp. 79-81 ◽  
Author(s):  
Brian E. Moore ◽  
Nathan P. Somers ◽  
Thomas W. Smith
Keyword(s):  
Amyloid Precursor Protein ◽  
Axonal Injury ◽  
Neurological Complications ◽  
Precursor Protein ◽  
Intrathecal Methotrexate ◽  
Nerve Roots ◽  
Marked Decline ◽  
Β Amyloid ◽  
The Brain ◽  
Biphenotypic Leukemia

Abstract We describe a 64-year-old woman with biphenotypic leukemia involving the meninges who received 2 doses of intrathecal methotrexate. Soon after treatment, the patient developed postural rigidity and a marked decline in mental status. The patient died of respiratory failure 1 month after methotrexate treatment was initiated. At autopsy, the brain was grossly normal. Routine microscopy showed no evidence of leukemic infiltrates or necrotizing lesions. However, when stained with β-amyloid precursor protein, multifocal axonal injury was evident in the brain, spinal cord, and nerve roots. Our findings show that immunohistochemical staining for β-amyloid precursor protein can effectively demonstrate axonal injury associated with methotrexate neurotoxicity, even when conventional staining procedures are negative. This technique may therefore reveal a possible pathologic substrate for some of the neurological complications seen in patients with methotrexate neurotoxicity.

scholarly journals Glial Expression of the β-Amyloid Precursor Protein (APP) in Global Ischemia

1995 ◽  
Vol 15 (4) ◽  
pp. 647-654 ◽  
Author(s):  
R. B. Banati ◽  
J. Gehrmann ◽  
C. Wießner ◽  
K.-A. Hossmann ◽  
G. W. Kreutzberg
Keyword(s):  
Amyloid Precursor Protein ◽  
Glial Cells ◽  
Global Ischemia ◽  
Precursor Protein ◽  
Double Immunofluorescence ◽  
Neuronal Necrosis ◽  
Activated Microglia ◽  
Β Amyloid ◽  
Immunofluorescence Labeling ◽  
The Brain

The β-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postishemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA1 and CA4 regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double-immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double-immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B4. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in astrocytes and microglia.

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