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P4–391: Correlations of neurobiologic abnormalities with clinical disabilities in Alzheimer disease (AD)
Author(s) -
Blass John P.,
Gibson Gary E.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2132
Subject(s) - synaptophysin , correlation , alzheimer's disease , autopsy , medicine , psychology , pathology , cerebral cortex , cognitive impairment , disease , neuroscience , immunohistochemistry , geometry , mathematics
Background: A variety of neurobiological abnormalities have been documented in Alzheimer disease, but it is not clear which of these relate closely enough to the clinical disability that ameliorating them is likely to help the patients. Objective(s): To obtain quantitative information on this problem. Methods: A comparison has been made of published values of the correlations between specific biological abnormalities and global cognitive impairment, as measured by standard psychological scales. Results: The closest correlation with clinical impairment was with overall cerebral glucose utilization, potentially accounting for over half of the variation in clinical disability (r 0.75, r2 56%). Decreased activity of the 3 irreversible enzymes of the Krebs tricarboxylic acid cycle was also high (r 0.654, r2 43%); in an alternative analysis, the sum of the r2 values for each of these three enzymes approached 100%. Among neuropathological findings, the closest correlation was with loss of immunoreactivity of the synaptic protein synaptophysin (r 0.57-0.67, r2 32%-44%). However, reported correlations with other synaptic markers were not significant in autopsy AD brain. Correlations with tangles were slightly lower (r 0.52-0.55, r2 27%-30%). Correlations with amyloid peptides were inconsistent: r 0.52 and r2 27% for plaques in midfrontal cortex, no significant relationship with plaque count in inferior parietal cortex or with amount of amyloid peptides by radioimmunoassay, and a significant negative correlation with amyloid peptides in CSF (r 0.69). Data was not found on quantitative correlations between global cognitive impairment and amount of (rather than simple presence of) oxidative stress or degree of inflammation. Conclusions: This analysis suggests that treatments directed to the functional abnormalities and specifically the deficiencies in brain metabolism may be more beneficial for AD patients than treatments directed to anatomic abnormalities such as loss of synaptophysin or accumulation of tangles or amyloid peptides. Preliminary clinical trials of this approach in humans suggest that further such studies are appropriate.