Nuclear microscope analysis in Alzheimer's and Parkinson's disease: A review

Abstract

The scanning nuclear microprobe (nuclear microscope) is becoming a powerful instrument for the accurate measurement of minor and trace elements in biological tissue. Using the simultaneously applied techniques of Scanning Transmission Ion Microscopy (STIM) to image features in the tissue, Particle induced X-ray emission (PIXE) to measure trace element concentrations, and Rutherford Backscattering Spectrometry (RBS) to characterize the tissue matrix, accurate elemental analysis at the parts per million level can be obtained for most elements. This review describes briefly the results obtained using the nuclear microscope for the elemental analysis of Alzheimer's and Parkinson's tissue. In Alzheimer's disease (AD) the identification and subsequent analysis of neuritic plaque cores in unstained tissue, yielded an absence of aluminium at the limit of 15 parts per million. Previous analyses involving stained sections were prone to misinterpretation due to aluminium contamination from the staining procedures. Elemental iron, calcium, phosphorus and sulphur were elevated both in the plaques and the AD background tissue compared to age matched controls. Preliminary analyses of neurofibrillary tangles stained with toluidine blue showed increased levels of calcium, although the staining procedure may have distorted the results due to element redistribution. In Parkinson's disease (PD) nuclear microscope studies have concentrated on measurements of iron in the substantia nigra (SN) region of the brain; iron was observed to be elevated by a factor 2 in MPTP induced Parkinsonism in African Green monkeys, and by a factor of 1.25 in 6-OHDA induced Parkinsonism in Sprague Dawley rats. These studies are consistent with other studies showing a general increase in the concentrations of iron associated with PD, and support the theory that iron mediated free radical production may enhance or accelerate the degeneration of dopaminergic cells through oxidative stress.