Higher atrophy rate of entorhinal cortex than hippocampus in AD.

OBJECTIVES: To determine if atrophy rates were higher for entorhinal cortex (ERC) than for hippocampus in Alzheimer disease (AD), to determine the relationship between hippocampal atrophy rate and memory impairment, and to compare atrophy rates of ERC and hippocampus in differentiating between patients with AD and cognitively normal (CN) controls. METHODS: Twenty patients with AD and 25 CN subjects had MRI scans and clinical evaluations twice approximately 1.9 years apart. ERC volumes were measured manually and hippocampal volumes were measured semiautomatically on volumetric T1-weighted MR images. RESULTS: In AD, the atrophy rate of ERC (7.1 +/- 3.2%/year) was higher (p < 0.02) than that of hippocampus (5.9 +/- 2.4%/year). Furthermore, memory deficit in mild AD, measured with the Delayed List Verbal Recall test, correlated significantly with atrophy rates of both ERC (r = -0.61) and hippocampus (r = -0.59). Atrophy rates of ERC and hippocampus were comparable in differentiating between AD and CN. Using atrophy rates of ERC or hippocampus to detect a 20% treatment effect with 90% power (p < 0.05) would require about 100 completed patients per arm in a 2-year study. CONCLUSION: The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.

CSF-tau, CSF-Abeta1-42, ApoE-genotype and clinical parameters in the diagnosis of Alzheimer's disease: combination of CSF-tau and MMSE yields highest sensitivity and specificity.

This study evaluated the sensitivity and specificity of the cerebrospinal fluid (CSF) levels of tau-protein, amyloid-beta-peptide 1-42 (Abeta1-42), ApoE-genotype and the degree of cognitive decline as diagnostic markers for Alzheimer's disease (AD). Data was obtained from 105 AD patients and 68 controls. Median CSF-tau levels were increased (512 pg/ml vs. 145 pg/ml, p<0.001) and Abeta1-42-levels were decreased (238.5 pg/ml vs. 310 pg/ml, p<0.001) in AD patients compared to controls. A weak correlation was found between CSF-Abeta1-42 and MMSE score (r=.245). Within all subjects, a correlation of CSF-Abeta1-42 (r=-.337) and CSF-tau (r=.384) with age was found. The combination of CSF-tau levels and MMSE revealed the highest sensitivity (92%) and specificity (87%). In summary, CSF-tau was a useful biological marker to discriminate AD from normal aging, neurological and psychiatric disorders. CSF-Abeta1-42 showed no additional benefit in discriminating patients from controls but might be useful for tracking the severity of the disease.

The microbial receptor CEACAM3 is linked to the calprotectin complex in granulocytes.

Engulfment of foreign pathogens is an evolutionary ancient host cell endocytic response. Signaling pathways effecting phagocytosis are divergent and largely depend on the structural features of the cell surface receptor utilized. CEACAM3, a member of the CD66 complex on human neutrophils, has been implicated as a cellular receptor promoting phagocytosis of microorganisms. The cytoplasmic domain of CEACAM3 (CEACAM3(cyt)) contains an immunoreceptor tyrosine-based activation motif. In this study we demonstrate that CEACAM3(cyt) is phosphorylated by protein kinase C, casein kinase I, and Src-kinase in vitro. To identify molecules binding to CEACAM3(cyt) in vivo, we used differentially phosphorylated recombinant expressed CEACAM cytoplasmic domains to isolate CEACAM3(cyt)-associated proteins from granulocyte extracts. Calprotectin, which modulates neutrophil integrin-mediated adhesion and leukocyte trafficking and displays antimicrobial activity, interacts specifically with CEACAM3(cyt). This interaction is calcium-modulated but independent of phosphorylation of CEACAM3(cyt). Although tyrosine-phosphorylated CEACAM3(cyt) binds and stimulates Src-kinases in vitro, no CEACAM3(cyt)-associated phosphokinase activity was copurified.

Cognitive dysfunction at baseline predicts symptomatic 1-year outcome in first-episode schizophrenics.

The present study addresses the consequences of cognitive disturbances on symptomatic outcome. Fifty-three first-episode schizophrenics were reassessed (n = 32) 1 year after admission. Simple regression analyses revealed that several self-perceived cognitive deficits at baseline as measured with the Frankfurt Complaint Questionnaire significantly predicted increased Brief Psychiatric Rating Scale global scores at follow-up (p = 0.05 to p = 0.005). A stepwise regression analysis proved memory dysfunction to be the strongest predictor of symptomatic worsening (p = 0.005). It is suggested that the exploration and treatment of neuropsychological deficits in schizophrenia is of great clinical importance with regard to its impact on both functional and symptomatic outcome in schizophrenia.