Recent cerebrospinal fluid biomarker studies of Alzheimer's disease.
ABSTRACT Alzheimer's disease is a progressive neurodegenerative disorder and the most common form of dementia. The disease is confirmed by the presence of neuritic plaques and neurofibrillary tangles in the cerebral cortex at autopsy, but the accuracy of antemortem diagnosis, especially at the early stages of the disease, is not ideal. Thus, there is a substantial need for the discovery and validation of diagnostic biomarkers. Many Alzheimer's disease biomarker discovery studies emphasize the analysis of cerebrospinal fluid (CSF) because of its close association with the brain. Here, we review recent mass spectrometry-based studies of Alzheimer's disease CSF, and additionally discuss issues associated with CSF in proteomics studies.
Article: Developing predictive CSF biomarkers-a challenge critical to success in Alzheimer's disease and neuropsychiatric translational medicine.[show abstract] [hide abstract]
ABSTRACT: The need to develop effective treatments for Alzheimer's disease has been confounded by repeated clinical failures where promising new chemical entities that have been extensively characterized in preclinical models of Alzheimer's disease have failed to show efficacy in the human disease state. This has been attributed to: the selection of drug targets that have yet to be shown as causal to the disease as distinct from being the result of the disease process, a lack of congruence in the animal models of Alzheimer's disease, wild-type and transgenic, to the human disease, and the enrollment of patients in proof of concept clinical trials who are at too advanced a stage of the disease to respond to any therapeutic. The development of validated biomarkers that can be used for disease diagnosis and progression is anticipated to improve patient enrollment in clinical trials, to develop new animal models and to identify new disease targets for drug discovery. The present review assesses the status of current efforts in developing CSF biomarkers for Alzheimer's disease and briefly discusses the status of CSF biomarker efforts in schizophrenia, depression, Parkinson's disease and multiple sclerosis.Biochemical pharmacology 02/2011; 81(12):1422-34. · 4.25 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.PLoS ONE 01/2012; 7(2):e31501. · 4.09 Impact Factor