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Brain Structure and Function
Published in: Brain Structure and Function 1/2018

01-01-2018 | Original Article

Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion

Authors: Jennifer A. Ross, Beverly A. S. Reyes, Steven A. Thomas, Elisabeth J. Van Bockstaele

Published in: Brain Structure and Function | Issue 1/2018

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Abstract

The locus coeruleus (LC)–norepinephrine (NE) system is an understudied circuit in the context of Alzheimer’s disease (AD), and is thought to play an important role in neurodegenerative and neuropsychiatric diseases involving catecholamine neurotransmitters. Understanding the expression and distribution of the amyloid beta (Aβ) peptide, a primary component of AD, under basal conditions and under conditions of NE perturbation within the coeruleo-cortical pathway may be important for understanding its putative role in pathological states. Thus, the goal of this study is to define expression levels and the subcellular distribution of endogenous Aβ with respect to noradrenergic profiles in the rodent LC and medial prefrontal cortex (mPFC) and, further, to determine the functional relevance of NE in modulating endogenous Aβ42 levels. We report that endogenous Aβ42 is localized to tyrosine hydroxylase (TH) immunoreactive somatodendritic profiles of the LC and dopamine-β-hydroxylase (DβH) immunoreactive axon terminals of the infralimbic mPFC (ILmPFC). Male and female naïve rats have similar levels of amyloid precursor protein (APP) cleavage products demonstrated by western blot, as well as similar levels of endogenous Aβ42 as determined by enzyme-linked immunosorbent assay. Two models of NE depletion, DSP-4 lesion and DβH knockout (KO) mice, were used to assess the functional relevance of NE on endogenous Aβ42 levels. DSP-4 lesioned rats and DβH-KO mice show significantly lower levels of endogenous Aβ42. Noradrenergic depletion did not change APP-cleavage products resulting from β-secretase processing. Thus, resultant decreases in endogenous Aβ42 may be due to decreased neuronal activity of noradrenergic neurons, or, by decreased stimulation of adrenergic receptors which are known to contribute to Aβ42 production by enhancing γ-secretase processing under normal physiological conditions.
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Metadata
Title
Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion
Authors
Jennifer A. Ross
Beverly A. S. Reyes
Steven A. Thomas
Elisabeth J. Van Bockstaele
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 1/2018
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-017-1489-9

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