The role of metallobiology and amyloid-ß peptides in Alzheimer's disease.

The biggest risk factor for Alzheimer's disease is the process of ageing, but the mechanisms that lead to the manifestation of the disease remain to be elucidated. Why age triggers the disease is unclear but an emerging theme is the inability for a cell to efficiently maintain many key processes such as energy production, repair, and regenerative mechanisms. Metal ions are essential to the metabolic function of every cell. This review will explore the role and reported changes in metal ions in Alzheimer disease, particularly the brain, blood and cerebral spinal fluid, emphasizing how iron, copper and zinc may be involved through the interactions with amyloid precursor protein, the proteolytically cleaved peptide amyloid-beta (Aß), and other related metalloproteins. Finally, we explore the monomeric makeup of possible Aß dimers, what a dimeric Aß species from Alzheimer's disease brain tissue is likely to be composed of, and discuss how metals may influence Aß production and toxicity via a copper catalyzed dityrosine cross-link.

A preliminary study of metalloproteins in CSF by CapLC-ICPMS and NanoLC-CHIP/ITMS.

Cerebrospinal fluid (CSF) has frequently been studied to explore the total metal concentrations in patients with neurodegenerative diseases. Some examples of neurologic diseases include but are not limited to intracerebral hemorrhage, intraventricular hemorrhage, traumatic brain injury, subarachnoid hemorrhage and hydrocephalus. In this study, however, a comprehensive approach was begun using metallomics methods. First, two molecular weight cutoff filters were used to separate CSF constituents by molecular weight. The remaining CSF was then separated with capillary liquid chromatography/normal bore liquid chromatography and analyzed with inductively coupled mass spectrometry (ICPMS). With this ICPMS screening, a possible iron associated protein was suggested by nanoliquid chromatography-CHIP/ion trap mass spectrometry (nanoLC-CHIP/ITMS) identification in conjunction with a Spectrum Mill database search. In this preliminary study, three different types of pooled CSF were partially characterized by their metal (Pb, Mg, Zn, Fe and Cu) containing species with suggestions for fuller studies. Chemical 'differences' in the CSF and metal constituents suggests some utility in this analysis for understanding some of the complications observed following subarachnoid hemorrhage.

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage.

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm.