Elevated cortical zinc in Alzheimer disease.
OBJECTIVE
To determine whether changes in brain biometals in Alzheimer disease (AD) and in normal brain tissue are tandemly associated with amyloid beta-peptide (Abeta) burden and dementia severity.


METHODS
The authors measured zinc, copper, iron, manganese, and aluminum and Abeta 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/mm(2). 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 beta-peptide accumulation and dementia severity in AD.
Religa
D
D
Neurotec, Experimental Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Strozyk
D
D
Cherny
R A
RA
Volitakis
I
I
Haroutunian
V
V
Winblad
B
B
Naslund
J
J
Bush
A I
AI
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D019216:Metals, Heavy / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism; D011180:Postmortem Changes; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology; D013223:Statistics as Topic; D015032:Zinc / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D019216:Metals, Heavy; D015032:Zinc