Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683–7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analysis of blood or cerebrospinal fluid (CSF). α‐Synuclein (α‐syn) protein has been linked to the pathogenesis of PD with the discovery of mutations in the gene encoding α‐syn in familial cases with early‐onset PD. Lewy bodies and Lewy neurites, which constitute the main pathological features in the brains of patients with sporadic PD and dementia with Lewy bodies, are formed by the conversion of soluble monomers of α‐syn into insoluble aggregates. We recently reported the presence of α‐syn in normal human blood plasma and in postmortem CSF. Here, we investigated whether α‐syn can be used as a biomarker for PD. We have developed a novel ELISA method that detects only oligomeric “soluble aggregates” of α‐syn. Using this ELISA, we report the presence of significantly elevated ( P =0.002) levels of oligomeric forms of α‐syn in plasma samples obtained from 34 PD patients compared with 27 controls; 52% (95% confidence intervals 0.353–0.687) of the PD patients displayed signals >0.5 OD with our ELISA assay in comparison to only 14.8% (95% confidence intervals 0.014 –0.281) for the control cases. An analysis of the test's diagnostic value revealed a specificity of 0.852 (95% confidence intervals 0.662– 0.958), sensitivity of 0.529 (95% confidence intervals 0.351–0.702) and a positive predictive value of 0.818 (95% confidence intervals 0.597–0.948). These observations offer new opportunities for developing diagnostic tests for PD and related diseases and for testing therapeutic agents aimed at preventing or reversing the aggregation of α‐syn.—El‐Agnaf, O. M. A., Salem, S. A., Paleologou, K. W., Curran, M. D., Gibson, M. J., Court, J. A., Schlossmacher, M. G., Allsop, D. Detection of oligomeric forms of α‐synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J. 20, 419 –425 (2006)

The repeated head trauma experienced by boxers can lead to the development of dementia pugilistica (DP)--punch drunk syndrome. The neuropathology of DP in a classic report by Corsellis et al describes the presence of numerous neurofibrillary tangles in the absence of plaques, in contrast to the profusion of tangles and plaques seen in Alzheimer's disease (AD). The DP cases used in that report were re-investigated with immunocytochemical methods and an antibody raised to the beta-protein present in AD plaques. We found that all DP cases with substantial tangle formation showed evidence of extensive beta-protein immunoreactive deposits (plaques). These diffuse "plaques" were not visible with Congo-red or standard silver stains. The degree of beta-protein deposition was comparable to that seen in AD. Our data indicate that the present neuropathological description of DP (tangles but no plaques) should be altered to acknowledge the presence of substantial beta-protein deposition (plaques). The molecular markers present in the plaques and tangles of DP are the same as those in AD. Similarities in clinical symptoms, distribution of pathology and neurochemical deficits also exist. Epidemiological studies have shown that head injury is a risk factor in AD. It is probable that DP and AD share common pathogenic mechanisms leading to tangle and plaque formation.