No abstract

Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer’s disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using β-amyloid 1–42 (Aβ42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Aβ42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-α, TGF-β₁, MIP-1α) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Aβ42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Aβ42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.

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.

No abstract

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon.