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NEUROLOGY 2006;67:69-75
© 2006 American Academy of Neurology

Elevated cortical zinc in Alzheimer disease

D. Religa, MD*, D. Strozyk, MD*, R. A. Cherny, PhD, I. Volitakis, BSc(Hons), V. Haroutunian, PhD, B. Winblad, MD, PhD, J. Naslund, PhD and A. I. Bush, MBBS, PhD

From Neurotec (D.R., B.W., J.N.), Experimental Geriatrics, Karolinska Institutet, Stockholm, Sweden; Medical Research Centre (D.R.), Polish Academy of Sciences, Warsaw, Poland; Department of Neurology (D.S.), Kennedy Center, Albert Einstein College of Medicine, Bronx, and Mount Sinai School of Medicine and Bronx VA Medical Center (V.H.), New York, NY, and Laboratory for Oxidation Biology (A.I.B.), Genetics and Aging Research Unit, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA; and Oxidation Biology Laboratory (R.A.C., I.V., A.I.B.), Mental Health Research Institute of Victoria, and Department of Pathology, University of Melbourne, Victoria, Australia.

Address correspondence and reprint requests to Dr Bush, Oxidation Biology Laboratory, Mental Health Research Institute of Victoria, 155 Oak St., Parkville, Victoria 3052, Australia; e-mail: abush{at}mhri.edu.au

Objective: To determine whether changes in brain biometals in Alzheimer disease (AD) and in normal brain tissue are tandemly associated with amyloid ß-peptide (Aß) burden and dementia severity.

Methods: The authors measured zinc, copper, iron, manganese, and aluminum and Aß levels in postmortem neocortical tissue from patients with AD (n = 10), normal age-matched control subjects (n = 14), patients with schizophrenia (n = 26), and patients with schizophrenia with amyloid (n = 8). Severity of cognitive impairment was assessed with the Clinical Dementia Rating Scale (CDR).

Results: There was a significant, more than twofold, increase of tissue zinc in the AD-affected cortex compared with the other groups. Zinc levels increased with tissue amyloid levels. Zinc levels were significantly elevated in the most severely demented cases (CDR 4 to 5) and in cases that had an amyloid burden greater than 8 plaques/mm2. Levels of other metals did not differ between groups.

Conclusions: Brain zinc accumulation is a prominent feature of advanced Alzheimer disease (AD) and is biochemically linked to brain amyloid ß-peptide accumulation and dementia severity in AD.

*Drs. Religa and Strozyk are co-first authors.

Supported by grants from the National Institute on Aging (RO1AG12686), the Alzheimer's Association, the American Health Assistance Foundation, the National Health and Medical Research Council of Australia, and the Australian Research Council (Federation Fellowship to A.I.B.), AG02219, AG05138, MH45212, the SADF, and Stiftelsen for Gamla Tjanarinnor.

Disclosure: The authors report no conflicts of interest.

Received December 7, 2005.

Accepted in final form March 20, 2006.


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