Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer's Disease Patient.

Amrutha Chilumuri,Nathaniel G N Milton,Amanda N Nercessian,Maria Ashioti

doi:10.1155/2013/879710

Amrutha Chilumuri, Nathaniel G N Milton + Show 2 more

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https://doi.org/10.1155/2013/879710

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Abstract

The pons region of the Alzheimer's disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject.

Highlights

The deposition of the amyloid-β (Aβ) peptide within plaques in the Alzheimer’s disease (AD) brain is a central feature of the disease pathology [1, 2]
A sequential pattern of Aβ deposition within different regions of the brain has been suggested as AD progresses [3,4,5,6]
The apparent resistance of the cerebellum and pons to neurodegenerative changes suggests that endogenous neuroprotective processes may play a role in these tissues

Summary

Introduction

The deposition of the amyloid-β (Aβ) peptide within plaques in the Alzheimer’s disease (AD) brain is a central feature of the disease pathology [1, 2]. A sequential pattern of Aβ deposition within different regions of the brain has been suggested as AD progresses [3,4,5,6]. In transgenic mice overexpressing the human amyloid precursor protein (APP) the Aβ deposition showed a similar sequential pattern, with the cerebellum and pons again the last to show Aβ deposits [7]. In a recent study kisspeptin (KP) peptides were suggested to have neuroprotective properties against Aβ plus related amyloid proteins [17]. The release of KP from human neuronal cells has been shown to be stimulated by Aβ [17] suggesting that in regions that express the KiSS-1 gene, which encodes for the KP peptides, there may be changes in KP levels in AD due to the elevations of Aβ

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