Copper involvement in glutamatergic transmission in physiology and disease as revealed by magnetoencephalography/electroencephalography (MEG/EEG) studies

  • Rosanna SquittiEmail author
  • Maria Luisa Malosio
  • Mauro Ciro Antonio Rongioletti
  • Franca Tecchio
Point of View


Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. The sporadic late onset form of the disease is a multifactorial complex disorder influenced by genetic and environmental factors. Evidence about the involvement of copper deregulation in AD is overwhelming, encompassing in vitro, experimental models (ref. 1 additional material), clinical, neurophysiological, genetic and meta-analyses studies. An overview of the most relevant findings with a focus on the plasticity phenomena as revealed by magnetoencephalography/electroencephalography (MEG/EEG) studies in living individuals is provided herein.

Brain copper homeostasis

Copper (also reported as Cu through the text) is an essential trace metal that is a required co-factor for the formation and function of many vital enzymes and pathways, such as for example hemoglobin (copper is an integral part of Aminolevulinic acid synthase -ALA synthase-, which is the key enzyme in heme synthesis) and...


Alzheimer’s disease Mild cognitive impairment Copper Magnetoencephalography/electroencephalography (MEG/EEG) synapse Glutammate 



MLM thanks 5 × 1000 (2016–2017) IRCCS Humanitas; KMN142 and KMN153 Ministry of Health. RS thanks Alzheimer’s Association for grant Program: Part the Cloud: Translational Research Funding for Alzheimer’s Disease (PTC); Project Title: Extenzin-based therapy for MCI subjects; Proposal Number: 602325; Award Number: PTC-19-602325 and Ricerca Finalizzata; this work was also supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population” (Prot. MIUR 2867 25.11.2011).

Compliance with ethical standards

Conflict of interest

RS is Scientific Officer of IGEA Pharma N.V.; she and has some shares in IGEA Pharma N.V., but does not receive monetary compensation. The others declare no conflict of interest.

Statement of human and animal rights

All experiments mentioned in the present Point of View conform to ‘The Code of Ethics’ of the World Medical Association (Declaration of Helsinki).

Informed consent

People signed informed consent before enrolment to the protocols approved by the respective Local Ethical Committees.

Supplementary material

40520_2019_1402_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 18 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.IRCCS Istituto Centro San Giovanni di Dio-FatebenefratelliBresciaItaly
  2. 2.Institute of Neuroscience, CNRMilanItaly
  3. 3.Laboratory of Pharmacology and Brain PathologyNeuro Center, Humanitas Clinical and Research Center-IRCCSRozzanoItaly
  4. 4.Department of Laboratory Medicine, Research and Development DivisionFatebenefratelli Hospital, Isola TiberinaRomeItaly
  5. 5.Let’s-ISTC-CNR and IRCCS Policlinico GemelliRomeItaly

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