Alzheimer's disease (AD) is a progressive neurodegenerative disorder with characteristic neuropathological changes of the brain. Great efforts have been undertaken to determine the progression of the disease and to monitor therapeutic interventions. Especially, the analysis of blood plasma had yielded incongruent results. Recently, Ray et al. (Nat. Med. 13, 2007, 1359f) identified changes of 18 signaling proteins leading to an accuracy of 90% in the diagnosis of AD. The aim of the present study was to examine 16 of these signaling proteins by quantitative Searchlight multiplex ELISA in order to determine their sensitivity and specificity in our plasma samples from AD, mild cognitive impairment (MCI), depression with and without cognitive impairment and healthy subjects. Quantitative analysis revealed an increased concentration in Biocoll isolated plasma of 5 out of these 16 proteins in MCI and AD patients compared to healthy subjects: EGF, GDNF and MIP1δ (in AD), MIP4 (in MCI) and RANTES (in MCI and AD). ROC analysis predicted a sensitivity of 65-75% and a specificity of 52-63% when comparing healthy controls versus MCI or AD. Depression without any significant cognitive deficits did not cause any significant changes. Depressed patients with significant cognitive impairment were not different from MCI patients. In conclusion, we detected a number of altered proteins that may be related to a disease specific pathophysiology. However, the overall expression pattern of plasma proteins could not be established as a biomarker to differentiate MCI from AD or from depression.

In this study, we explored to what extent brain abnormalities can be identified in specific brain structures of patients suffering from late onset depression. We examined the structural difference in regional gray and white matter volume between 14 community-dwelling patients suffering from geriatric depression and 20 age-matched non-depressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging. All subjects also underwent an extensive neuropsychological assessment. Compared with control subjects, patients with depression were impaired in measures of verbal and visual memory, construction, executive ability, and information-processing speed. VBM of gray matter revealed a significant decrease of volume in the right rostral hippocampus, in the right amygdala and in the medial orbito-frontal cortex (gyrus rectus) bilaterally. In the correlation analysis of gray matter volume with the score of the geriatric depression scale, we observed a negative correlation with the medial orbito-frontal cortex (gyrus rectus) bilaterally. There were no differences in white matter volumes between patients with depression and healthy control subjects. The most important limitation of this study was sample size. A larger sample size may have improved detection of changes not reaching significance. Furthermore, our results may not be generalizable across depression severity or to hospitalized patients. The findings are consistent with our hypothesis that depression in the elderly is associated with local gray matter dysfunction.