title: 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.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors.forename: Tina
authors.initials: T
authors.lastname: Bilousova
authors.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors.forename: Karen
authors.initials: K
authors.lastname: Taylor
authors.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Emirzian
authors.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Gylys
authors.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Frautschy
authors.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cole
authors.affiliation: Department of Neurology, David Geffen School of Medicine, at UCLA, Los Angeles, CA, United States; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States. Electronic address: eteng@ucla.edu.
authors.forename: Edmond
authors.initials: E
authors.lastname: Teng
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000375:Aging / Q000097:blood / Q000378:metabolism*; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D011956:Receptors, Cell Surface / Q000097:blood / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011956:Receptors, Cell Surface; C107687:neuronal pentraxin receptor; D051722:ADAM Proteins; D000072198:ADAM17 Protein
keywords: Alzheimer's disease; Biomarker; Cortex; Hippocampus; Neuronal pentraxin; Plasma; Synaptic function; Transgenic