Non-Ceruloplasmin Copper Identifies a Subtype of Alzheimer’s Disease (CuAD): Characterization of the Cognitive Profile and Case of a CuAD Patient Carrying an RGS7 Stop-Loss Variant

Autor:	Rosanna Squitti, Claudio Catalli, Laura Gigante, Massimo Marianetti, Mattia Rosari, Stefania Mariani, Serena Bucossi, Gioia Mastromoro, Mariacarla Ventriglia, Ilaria Simonelli, Vincenzo Tondolo, Parminder Singh, Ashok Kumar, Amit Pal, Mauro Rongioletti
Rok vydání:	2023
Předmět:	Inorganic Chemistry Organic Chemistry General Medicine Physical and Theoretical Chemistry Molecular Biology Alzheimer’s disease ceruloplasmin copper non-bound ceruloplasmin copper metals dementia executive functions dopamine Iron G-protein RGS7 stop-loss mutation Spectroscopy Catalysis Computer Science Applications
Zdroj:	International Journal of Molecular Sciences; Volume 24; Issue 7; Pages: 6377
ISSN:	1422-0067
DOI:	10.3390/ijms24076377
Popis:	Alzheimer’s disease (AD) is a type of dementia whose cause is incompletely defined. Copper (Cu) involvement in AD etiology was confirmed by a meta-analysis on about 6000 participants, showing that Cu levels were decreased in AD brain specimens, while Cu and non-bound ceruloplasmin Cu (non-Cp Cu) levels were increased in serum/plasma samples. Non-Cp Cu was advocated as a stratification add-on biomarker of a Cu subtype of AD (CuAD subtype). To further circumstantiate this concept, we evaluated non-Cp Cu reliability in classifying subtypes of AD based on the characterization of the cognitive profile. The stratification of the AD patients into normal AD (non-Cp Cu ≤ 1.6 µmol/L) and CuAD (non-Cp Cu > 1.6 µmol/L) showed a significant difference in executive function outcomes, even though patients did not differ in disease duration and severity. Among the Cu-AD patients, a 76-year-old woman showed significantly abnormal levels in the Cu panel and underwent whole exome sequencing. The CuAD patient was detected with possessing the homozygous (c.1486T > C; p.(Ter496Argext*19) stop-loss variant in the RGS7 gene (MIM*602517), which encodes for Regulator of G Protein Signaling 7. Non-Cp Cu as an add-on test in the AD diagnostic pathway can provide relevant information about the underlying pathological processes in subtypes of AD and suggest specific therapeutic options.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a7dcc51c4335376e24496ab12750f31 https://doi.org/10.3390/ijms24076377 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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