TY - JOUR
T1 - Zinc therapy in early alzheimer’s disease
T2 - Safety and potential therapeutic efficacy
AU - Squitti, Rosanna
AU - Pal, Amit
AU - Picozza, Mario
AU - Avan, Abofazl
AU - Ventriglia, Mariacarla
AU - Rongioletti, Mauro C.
AU - Hoogenraad, Tjaard
N1 - Funding Information:
Funding: This work was supported by the Italian Ministry of Health funded this study (Ricerca Corrente; RS). The study is also funded by the Alzheimer’s Association Part the Cloud: Translational Research Funding for Alzheimer’s Disease (PTC) PTC-19-602325, EudraCT 2019-000604-15 (RS).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - Zinc therapy is normally utilized for treatment of Wilson disease (WD), an inherited condition that is characterized by increased levels of non-ceruloplasmin bound (‘free’) copper in serum and urine. A subset of patients with Alzheimer’s disease (AD) or its prodromal form, known as Mild Cognitive Impairment (MCI), fail to maintain a normal copper metabolic balance and exhibit higher than normal values of non-ceruloplasmin copper. Zinc’s action mechanism involves the induction of intestinal cell metallothionein, which blocks copper absorption from the intestinal tract, thus restoring physiological levels of non-ceruloplasmin copper in the body. On this basis, it is employed in WD. Zinc therapy has shown potential beneficial effects in preliminary AD clinical trials, even though the studies have missed their primary endpoints, since they have study design and other important weaknesses. Nevertheless, in the studied AD patients, zinc effectively decreased non-ceruloplasmin copper levels and showed potential for improved cognitive performances with no major side effects. This review discusses zinc therapy safety and the potential therapeutic effects that might be expected on a subset of individuals showing both cognitive complaints and signs of copper imbalance.
AB - Zinc therapy is normally utilized for treatment of Wilson disease (WD), an inherited condition that is characterized by increased levels of non-ceruloplasmin bound (‘free’) copper in serum and urine. A subset of patients with Alzheimer’s disease (AD) or its prodromal form, known as Mild Cognitive Impairment (MCI), fail to maintain a normal copper metabolic balance and exhibit higher than normal values of non-ceruloplasmin copper. Zinc’s action mechanism involves the induction of intestinal cell metallothionein, which blocks copper absorption from the intestinal tract, thus restoring physiological levels of non-ceruloplasmin copper in the body. On this basis, it is employed in WD. Zinc therapy has shown potential beneficial effects in preliminary AD clinical trials, even though the studies have missed their primary endpoints, since they have study design and other important weaknesses. Nevertheless, in the studied AD patients, zinc effectively decreased non-ceruloplasmin copper levels and showed potential for improved cognitive performances with no major side effects. This review discusses zinc therapy safety and the potential therapeutic effects that might be expected on a subset of individuals showing both cognitive complaints and signs of copper imbalance.
KW - Alzheimer’s disease
KW - Copper
KW - Efficacy
KW - Mild cognitive impairment
KW - Wilson disease safety
KW - Zinc therapy
UR - http://www.scopus.com/inward/record.url?scp=85089408074&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089408074&partnerID=8YFLogxK
U2 - 10.3390/biom10081164
DO - 10.3390/biom10081164
M3 - Review article
C2 - 32784855
AN - SCOPUS:85089408074
VL - 10
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 8
M1 - E1164
ER -