ISSN 1758-2024 10.2217/NMT.12.59 © 2012 Future Medicine Ltd Neurodegen. Dis. Manage. (2012) 2(6), 557–559 Due caution must be exercised while making definitive statements about a substance as integral to the butter substitute industry as diacetyl (DA). Adequate justice to the question in the title requires substantiated comment on the question’s four intrinsic components. Two components can be answered with relative facility: what is the theoretical link of Alzheimer’s disease (AD) to DA? In addition, why is DA different from other chemically similar toxic substances, which are destroyed easily by the human body? However, rather involved is the address of two more important questions: what levels of DA suffice to initiate AD pathogenesis? What types of exposure cause the accumulation of toxic DA levels? AD pathology is biochemically and morphologically diverse, and is yet incompletely characterized. Two well-recognized features are the aggregation of the naturally occurring amyloid-b (Ab) peptide into pathological plaques, and the intraneuronal accumulation of hyperphosphorylated forms of the normally occurring tau protein (which forms neurofibrillary tangles) [1]. Although it is understood the underlying causes of such pathologies are in a constant state of flux, a ‘tilt’ in the balance between oxidative and reductive reactions toward the former has been unequivocally proven by many well-established groups to be present in the AD-afflicted brain [2]. Oxidative excess (oxidative stress) is expressed within the AD-afflicted brain as either excess free radicals, or excess reactive carbonyl species (RCSs), the latter being of relevance to this discussion. RCSs result from glucose and amino acid catabolism. Methylglyoxal (MG), a RCS, produced by neurons in large quantities, induces aggregation of Ab peptide into soluble toxic aggregates and insoluble toxic plaques [3]. MG also potentiates Ab’s toxicity toward neurons. Excesses of MG are normally destroyed by the glyoxalase (GLO) enzyme system, which utilizes ubiquitous glutathione and converts MG to the nontoxic lactate. Insufficient GLO activity in AD underscores the relevance of excess MG to AD pathogenesis [4]. DA is a close structural cousin of MG, in which one of MG’s hydrogens is replaced with a methyl group. This seemingly minor difference confers upon DA some rather worrisome capabilities. We have shown