Parallel age-associated changes in brain and plasma neuronal pentraxin receptor levels in a transgenic APP/PS1 rat model of Alzheimer's disease.

Abstract

Neuronal pentraxin receptor (NPR) is a synaptic protein implicated in AMPA receptor trafficking at excitatory synapses. Since glutamate neurotransmission is disrupted in Alzheimer's disease (AD), NPR levels measured from plasma represent a potential biomarker for synaptic dysfunction associated with AD. We sought to determine the relationship between AD pathology and brain and plasma NPR levels by examining age-associated NPR levels in these compartments in a transgenic APP/PS1 rat model of AD. NPR levels in cortical homogenate were similar in wild-type (Wt) and APP/PS1 rats at 3 months of age (prior to Aβ plaque deposition), but significantly increased in APP/PS1 rats by 9 and 18-20 months of age (after the onset of plaque deposition). These age-dependent differences were driven by proportional increases in NPR in membrane-associated cortical fractions. Genotype-related differences in NPR expression were also seen in the hippocampus, which exhibits significant Aβ pathology, but not in the cerebellum, which does not. Plasma analyses revealed increased levels of a 26 kDa NPR fragment in APP/PS1 rats relative to Wt rats by 18-20 months of age, which correlated with the levels of full-length NPR in cortex. Our findings indicate that cerebral accumulation of NPR and Aβ occurs with similar temporal and regional patterns in the APP/PS1 model, and suggest that a 26 kDa plasma NPR fragment may represent a peripheral biomarker of this process.

• Authors: Tina Bilousova, Karen Taylor, Ana Emirzian, Raymond Gylys, Sally A Frautschy, Gregory M Cole, Edmond Teng
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 74 Pg. 32-40 (Feb 2015) ISSN: 1095-953X [Electronic] United States
• PMID: 25449907 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• APP protein, human
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• PSEN1 protein, human
• Presenilin-1
• Receptors, Cell Surface
• neuronal pentraxin receptor
• ADAM Proteins
• ADAM17 Protein

Topics

• ADAM Proteins (metabolism)
• ADAM17 Protein
• Aging (blood, metabolism)
• Alzheimer Disease (blood, metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics, metabolism)
• Animals
• Blotting, Western
• Brain (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Humans
• Maze Learning (physiology)
• Presenilin-1 (genetics, metabolism)
• Rats, Sprague-Dawley
• Rats, Transgenic
• Receptors, Cell Surface (blood, metabolism)