Absence of aluminium in neurofibrillary tangles in Alzheimer’s disease Jagoda Makjanic a, *, Brendan McDonald b , Christopher Philip Li-Hsian Chen c , Frank Watt a a Nuclear Microscopy Group, Department of Physics, National University of Singapore, Lower Kent Ridge Road, 119260 Singapore, Singapore b Department of Neuropathology, University of Oxford, Oxford, UK c Department of Neurology, Singapore General Hospital, Singapore, Singapore Received 13 October 1997; received in revised form 5 December 1997; accepted 5 December 1997 Abstract Using the new technique of nuclear microscopy, aluminium is not detected in pyramidal neurons in brain tissue from Alzhei- mer’s disease (AD) patients. The analytical technique of nuclear microscopy can simultaneously image and analyse features in unstained and untreated tissue sections. In tissue which had been previously subjected to conventional procedures such as fixation and osmication, aluminium was observed in both neurons and surrounding tissue. This result shows that the analysis of tissue prepared using conventional chemical techniques may produce contamination or elemental redistribution, and supports our previous investigations which implied that aluminium is not involved in the aetiology of AD. In addition, significant increases in iron, phosphorus and sulphur concentrations were noted between neurons from Alzheimer tissue and neurons from age- matched controls, and between the supporting Alzheimer tissue and supporting control tissue, implying an overall increase in these elements. No significant increase in calcium was observed between neurons from Alzheimer tissue and neurons from age- matched controls.  1998 Elsevier Science Ireland Ltd. Keywords: Aluminium; Alzheimer’s disease; Neurofibrillary tangles; Nuclear microscopy Alzheimer’s disease (AD) is a progressive degenerative disease which is neuropathologically characterised by the occurrence of a minimum density of neurofibrillary tangles and neuritic plaques in the hippocampus and association cortex of the brain [9,14]. Whether or not aluminium plays a role in the aetiology of AD is still controversial. Recent epidemiological evidence pointing to a correlation between the occurrence of AD and increased aluminium level in drinking water [13] has been supported by analytical findings that aluminium concentrations are increased in the cerebral cortex of AD patients compared with age-matched controls [20]. This evidence is, however, counterbalanced by studies with different findings [1,5]. The most direct evidence of aluminium involvement in AD remains the detection of aluminium in situ in neurofi- brillary tangles (NFTs), bundles of paired helical filaments which develop in the cytoplasm of affected neurons, subse- quently leading to cell death. In addition, aluminium has also been detected in neuritic plaques, extracellular struc- tures composed of dense amyloid cores surrounded by a halo of abnormal neurites. Several groups have reported the presence of aluminium and silicon in plaque cores [2,4], while others have been unable to detect any correla- tion between these elements and neuritic plaques [3,8]. Similar inconsistencies exist in studies into elemental com- position of NFTs. Using the analytically sensitive but non- quantitative technique of laser microprobe mass analysis (LMMA), Good et al. [6] have detected significantly increased aluminium and iron levels in NFTs. In addition, recent electron microscope analyses of isolated lipofuscin granules, normally present in both neurofibrillary tangles and neuritic plaques, have indicated the presence of alu- mino-silicates [17]. Jacobs et al. [7] were unable to detect aluminium in either plaque cores or NFT-containing neu- rons. Again using LMMA, Lovell et al. [11] measured low Neuroscience Letters 240 (1998) 123–126 0304-3940/98/$19.00  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(97)00940-3 * Corresponding author. Tel.: +65 8742625; fax: +65 7776126; e-mail: phyjm@leonis.nus.edu.sg