Cortical biochemistry in MCI and Alzheimer disease: lack of correlation with clinical diagnosis.
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 Abeta, 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 Abeta and tau, as well as tissue isoprostanes, from each brain region analyzed did not correlate with the clinical diagnosis proximate to death, but insoluble Abeta and 8,12-iso-iPF(2alpha)-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, Abeta, and isoprostane do not reflect the onset of clinical dementia.
Forman
M S
MS
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd., 605B Stellar-Chance Building, Philadelphia, PA 19104, USA. formanm@mail.med.upenn.edu
Mufson
E J
EJ
Leurgans
S
S
Pratico
D
D
Joyce
S
S
Leight
S
S
Lee
V M-Y
VM
Trojanowski
J Q
JQ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D028421:Isoprostanes; D016875:tau Proteins