Alzheimer’s Disease and Age-Related Changes in the Cu Isotopic Composition of Blood Plasma and Brain Tissues of the APP[sup.NL-G-F] Murine Model Revealed by Multi-Collector ICP-Mass Spectrometry

• Published in: Biology (Basel, Switzerland) Switzerland), 2023-06, Vol.12 (6)
• Main Authors: Hobin, Kasper, Costas-Rodríguez, Marta, Van Wonterghem, Elien, Vandenbroucke, Roosmarijn E, Vanhaecke, Frank
• Format: Article
• Language: English
• Subjects: Advertising executives; Alzheimer's disease; Analysis; Brain; Ethylenediaminetetraacetic acid; Genetic engineering; Spectrum analysis
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12060857

Alzheimer's disease is the most prevalent form of dementia and is associated with multiple alterations in biological processes. The most profound changes consist of the formation of two types of protein aggregations, called β-amyloid plaques and neurofibrillary tangles of tau proteins. Different biologically relevant metals are believed to play a role during the development of Alzheimer's disease, including copper. In Alzheimer's disease, copper has been reported to interact with β-amyloid plaques and neurofibrillary tangles, while in addition its homeostasis and metabolism are known to be affected. Therefore, Cu was investigated in a murine model mimicking Alzheimer's disease. These mice were genetically manipulated, resulting in the presence of typical Alzheimer's disease symptoms. By making use of two inductively coupled plasma-mass spectrometry (ICP-MS) based analysis techniques, the Cu concentration and the ratio between the natural [sup.65]Cu and [sup.63]Cu isotopes ([sup.65]Cu/[sup.63]Cu) were determined in blood plasma and four different brain regions-brain stem, cerebellum, cortex, and hippocampus-of young and aged Alzheimer's mice and age-matched healthy controls. The Cu concentration in blood plasma was significantly altered in response to both age- and Alzheimer's-related effects, whereas the blood plasma Cu isotope ratio was affected in the Alzheimer's-affected mice only. Both the brain stem and cerebellum showed changes in Cu concentration and [sup.65]Cu/[sup.63]Cu isotope ratio as a result of ageing and the development of Alzheimer's disease. Finally, a correlation was observed between the [sup.65]Cu/[sup.63]Cu isotope ratio in the cerebellum and blood plasma. Determination of Cu concentration and isotope ratio is therefore a relevant tool to unravel the role of Cu in ageing and Alzheimer's disease. Alzheimer's' disease (AD) is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary tangles of tau protein in the brain. Aβ plaques are formed by the cleavage of the β-amyloid precursor protein (APP). In addition to protein aggregations, the metabolism of the essential mineral element Cu is also altered during the pathogenesis of AD. The concentration and the natural isotopic composition of Cu were investigated in blood plasma and multiple brain regions (brain stem, cerebellum, cortex, and hippocampus) of young (3-4 weeks) and aged (27-30 weeks) APP[sup.NL-G-F] knock-in mice and wild-type controls to assess potential alterat