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NEUROLOGY 2007;68:757-763
© 2007 American Academy of Neurology

Cortical biochemistry in MCI and Alzheimer disease

Lack of correlation with clinical diagnosis

M. S. Forman, MD, PhD, E. J. Mufson, PhD, S. Leurgans, PhD, D. Pratico, MD, S. Joyce, BS, S. Leight, BS, V. M.-Y. Lee, PhD and J. Q. Trojanowski, MD, PhD

From the Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (M.S.F., S.J., S.L., V.M.-Y.L., J.Q.T.), Institute on Aging (M.S., V.M.-Y.L., J.Q.T.), and Department of Pharmacology (D.P.), University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Neurological Sciences (E.J.M., S.L.), Rush University Medical Center, Chicago, IL.

Address correspondence and reprint requests to Dr. Mark S. Forman, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd., 605B Stellar-Chance Building, Philadelphia, PA 19104; e-mail: formanm{at}mail.med.upenn.edu

Objective: Mild cognitive impairment, hypothesized to be prodromal Alzheimer disease (AD), shows abundant senile plaques and neurofibrillary tangles, but its biochemical correlates remain undefined.

Methods: Biochemical profiles of Aß, tau, {alpha}-synuclein, and oxidative pathologies were characterized in middle frontal gyrus, inferior parietal cortex, and entorhinal cortex in postmortem frozen brains from subjects diagnosed antemortem with no cognitive impairment, mild cognitive impairment, or AD.

Results: Insoluble Aß and tau, as well as tissue isoprostanes, from each brain region analyzed did not correlate with the clinical diagnosis proximate to death, but insoluble Aß and 8,12-iso-iPF2{alpha}-VI levels from gray matter of all brain regions correlated strongly with the burden of AD pathology, whereas insoluble tau did not.

Conclusions: The biochemical alterations in cortical tau, Aß, and isoprostane do not reflect the onset of clinical dementia.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 6 issue to find the title link for this article.

Supported by grants from the NIH (P01 AG14449, P30 AG10161, RO1 AG10688, PO1 AG09466, and K08 AG20073).

Disclosure: The authors report no conflicts of interest.

Received March 8, 2006. Accepted in final form November 8, 2006.




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[Abstract] [Full Text] [PDF]


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