Excess Copper in Alzheimer Disease but Not in Frontotemporal Lobar Degeneration: Next-Generation Sequencing Study of ATP7B Gene in Patients Typified by High Copper. (21st September 2018)

• Record Type: Journal Article
• Authors: Rongioletti, Mauro; Fostinelli, Silvia; Ghidoni, Roberta; Benussi, Luisa; Binetti, Giuliano; Siotto, Mariacristina; Papa, Fabrizio; Vaccarella, Cinzia
• Is Part Of: American journal of clinical pathology. Volume 150(2018)Supplement 1
• Page Start: S65
• Page End: S66
• Publication Date: 2018-09-21
• Subjects: Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqy092.161
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Objectives: Copper failure is the cause of Wilson disease (WD), a rare disorder typified by increased levels of copper nonbound to ceruloplasmin (non-Cp Cu) and caused by mutations in the ATP7B gene, a copper transporter at the trans-Golgi network of the hepatocyte. Non-Cp Cu increases also in Alzheimer disease (AD), a multifactorial disorder and the main form of dementia in the elderly. Recent meta-analyses indicate reduced levels of copper in the brain, increased levels in the serum, and the expansion of a pool of non-Cp Cu, which typifies a subgroup of AD. However, a study evaluating copper changes in other neurodegenerative forms of dementia has not yet been performed. Methods: In this study, we assessed copper, ceruloplasmin, copper not bound to ceruloplasmin, and copper to ceruloplasmin ratio in 85 patients affected by frontotemporal lobar degeneration (FTLD), 60 AD patients, and 55 healthy controls. Data were analyzed through multivariate ANOVA models, taking into account age and sex as covariates and the stratification for FTLD clinical variants, after calculating power analysis to ensure the reliability of the conclusions drawn. A next-generation sequencing (NGS) study to search for specific ATP7B AD mutations on patients typified by increased values of non-Cp Cu has been carried out. Results: The study revealed no difference between FTLD and healthy controls, while AD had increased values of non-Cp Cu. In the NGS study, we expect to detect a difference in the biochemical variables among genetic groups of at least 60%. With such expected changes, the size n = 60 is sufficient to detect a difference between genetic groups with a power of higher than 90% (0<0.05). Conclusion: Excess non-Cp Cu is not a common signature of dementia but it appears specific for AD.