Nuclear microscopy in Alzheimer's disease

The elemental composition of the two types of brain lesions which character ise Alzheimer's disease (AD) has been the subject of intense scrutiny over the last decade, ever since it was proposed that inorganic trace elements, particularly aluminium, might be implicated in the pathogenesis of the dise ase. The major evidence for this involvement was the detection of aluminium in the characteristic lesions of the AD brain; neuritic plaques and neurof ibrillary tangles (NFTs). Using the powerful combination of Particle-Induce d X-ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS) and S canning Transmission Ion Microscopy (STIM), it is possible to image and ana lyse structures in brain sections without recourse to chemical staining. Pr evious results on elemental composition of senile plaques indicated the abs ence of aluminium at the 15 parts per million level. We have more recently focused on the analysis of neurofibrillary tangles (NFTs), destructive stru ctural defects within neurons. Imaging and analysis of neurons in brain tis sue presented a greater challenge due to the small dimensional size compare d with the plaques. We describe the methodology and the results of imaging and analysing neurons in brain tissue sections using Nuclear Microscopy. Ou r results show that aluminium is not present in either neurons or surroundi ng tissue in unstained sections at the 20 ppm level, but can be observed in stained sections. We also report elemental concentrations showing signific ant elevations of phosphorus, sulphur, chlorine, iron and zinc. (C) 1999 El sevier Science B.V. All rights reserved.