It is important to be able to characterise foods and feedstuffs according to their available amino acid contents. This involves being able to determine amino acids chemically and the conduct of bioassays to determine amino acid digestibility and availability. The chemical analysis of amino acids is not straightforward and meticulousness is required to achieve consistent results. In particular and for accuracy, the effect of hydrolysis time needs to be accounted for. Some amino acids (for example, lysine) can undergo chemical modification during the processing and storage of foods, which interferes with amino acid analysis. Furthermore, the modified amino acids may also interfere with the determination of digestibility. A new approach to the determination of available lysine using a modified in vivo digestibility assay is discussed. Research is required into other amino acids susceptible to structural damage. There is recent compelling scientific evidence that bacterial activity in the small intestine of animals and man leads to the synthesis and uptake of dietary essential amino acids. This has implications for the accuracy of the ileal-based amino acid digestibility assay and further research is required to determine the extent of this synthesis, the source of nitrogenous material used for the synthesis and the degree of synthesis net of amino acid catabolism. Although there may be potential shortcomings in digestibility assays based on the determination of amino acids remaining undigested at the terminal ileum, there is abundant evidence in simple-stomached animals and growing evidence in human subjects that faecal-based amino acid digestibility coefficients are misleading. Hindgut microbial metabolism significantly alters the undigested dietary amino acid profile. The ileal amino acid digestibility bioassay is expected to be more accurate than its faecal-based counterpart, but correction of the ileal amino acid flow for amino acids of endogenous origin is necessary. Approaches to correcting for the endogenous component are discussed.

Food consumption patterns are influenced by a number of factors, including social and cultural factors. It is difficult to effect dietary change, and one possible barrier to dietary change is optimistic bias. Research indicates that individuals tend to believe that they are less likely to experience negative events, and more likely to experience positive events than their peers; this phenomenon is known as optimistic bias. It has been argued that optimistic bias may have a negative impact both on self-protective behaviour and on efforts to promote risk-reducing behaviours. The present article reviews the literature investigating optimistic bias specifically in the food domain. The review indicated that many food and nutrition issues are associated with optimistic bias. This has important implications for health-promotion activities in the food domain. The paper also describes key aspects of the methodology used to investigate optimistic bias and details the conditions under which optimistic bias has been demonstrated. The importance of identifying the causes of optimistic bias is discussed, and empirical attempts designed to reduce optimistic bias by countering the causes are reviewed. Finally, directions for future research are suggested.

Resistant starch (RS) is defined as ‘the sum of starch and products of starch degradation not absorbed in the small intestine of healthy individuals’. This basic definition includes different types of starches that (1) are physically inaccessible, usually due to an encapsulation in intact cell walls, or (2) are naturally highly resistant to mammalian α-amylase, or (3) have been modified by hydrothermic treatments then retrograded. Interest in RS has increased significantly during the last two decades, mostly due to its capacity to produce a large amount of butyrate all along the colon. Butyrate has been observed to have a range of effects on cell metabolism, differentiation and cell growth as well as inhibition of a variety of factors that underlie the initiation, progression and growth of colon tumours. The physiological definition of RS, which seems to be nearly consensual, raises a difficulty in proper analytical quantification of RS. A number of methods have, however, been proposed and provide similar values for the RS content in most of the starch types and starchy foods. It seems, however, that some starches, proven to be partly resistant according to in vivo investigations on ileostomy subjects, could not be quantified by most of these methods. This may be due to a widespread use of glucoamylase during the first steps of these methods. Accordingly, there is an international debate on health aspects of RS and on how to quantify the RS content of food products. The present review describes aspects of classification of RS, past and current consumption, physiological effects and analytical aspects, and concludes with impacts on food and product labelling.

Abstract Polyols are hydrogenated carbohydrates used as sugar replacers. Interest now arises because of their multiple potential health benefits. They are non-cariogenic (sugar-free tooth-friendly), low-glycaemic (potentially helpful in diabetes and cardiovascular disease), low-energy and low-insulinaemic (potentially helpful in obesity), low-digestible (potentially helpful in the colon), osmotic (colon-hydrating, laxative and purifying) carbohydrates. Such potential health benefits are reviewed. A major focus here is the glycaemic index (GI) of polyols as regards the health implications of low-GI foods. The literature on glycaemia and insulinaemia after polyol ingestion was analysed and expressed in the GI and insulinaemic index (II) modes, which yielded the values: erythritol 0, 2; xylitol 13, 11; sorbitol 9, 11; mannitol 0, 0; maltitol 35, 27; isomalt 9, 6; lactitol 6, 4; polyglycitol 39, 23. These values are all much lower than sucrose 65, 43 or glucose 100, 100. GI values on replacing sucrose were independent of both intake (up to 50 g) and the state of carbohydrate metabolism (normal, type 1 with artificial pancreas and type 2 diabetes mellitus). The assignment of foods and polyols to GI bands is considered, these being: high (> 70), intermediate (> 55–70), low (> 40–55), and very low (< 40) including non-glycaemic; the last aims to target particularly low-GI-carbohydrate-based foods. Polyols ranged from low to very low GI. An examination was made of the dietary factors affecting the GI of polyols and foods. Polyol and other food GI values could be used to estimate the GI of food mixtures containing polyols without underestimation. Among foods and polyols a departure of II from GI was observed due to fat elevating II and reducing GI. Fat exerted an additional negative influence on GI, presumed due to reduced rates of gastric emptying. Among the foods examined, the interaction was prominent with snack foods; this potentially damaging insulinaemia could be reduced using polyols. Improved glycated haemoglobin as a marker of glycaemic control was found in a 12-week study of type 2 diabetes mellitus patients consuming polyol, adding to other studies showing improved glucose control on ingestion of low-GI carbohydrate. In general some improvement in long-term glycaemic control was discernible on reducing the glycaemic load via GI by as little as 15–20 g daily. Similar amounts of polyols are normally acceptable. Although polyols are not essential nutrients, they contribute to clinically recognised maintenance of a healthy colonic environment and function. A role for polyols and polyol foods to hydrate the colonic contents and aid laxation is now recognised by physicians. Polyols favour saccharolytic anaerobes and aciduric organisms in the colon, purifying the colon of endotoxic, putrefying and pathological organisms, which has clinical relevance. Polyols also contribute towards short-chain organic acid formation for a healthy colonic epithelium. Polyol tooth-friendliness and reduced energy values are affirmed and add to the potential benefits. In regard to gastrointestinal tolerance, food scientists and nutritionists, physicians, and dentists have in their independent professional capacities each now described sensible approaches to the use and consumption of polyols.

Despite continued efforts to prevent and control food-borne illness it remains a major cause of morbidity and mortality throughout the world. The problem is made worse by the continuous threat from emerging pathogens that can evolve to adapt to the different environments resulting from ongoing changes in farming or food production. The present review discusses the impact of genomics and post-genomic technologies on research in the area of food-borne bacterial pathogens. Genomics research is moving at a fast pace and these are exciting times for microbial research. The genome sequences of approximately ninety bacterial genomes have recently been completed and genome sequences are already available for several food-borne pathogens and closely related species. Comparative genomics is providing new insights into mechanisms of bacterial evolution and has helped in determining virulence factors of pathogens. Genomics has also provided tools such as DNA microarrays that can be used to examine the genetic composition and whole genome expression profiles of bacterial strains by hybridisation of fluorescently labelled DNA. This is helping to identify genes associated with particular phenotypes such as virulence and host preference, and to identify genes in uncharacterised genomes of closely related organisms. Microarrays are also being developed for the detection of food-borne pathogens and investigation of the evolutionary relationship between different species of bacteria. The review concludes with a discussion of the use of functional genomics tools to investigate bacterial responses to environmental stresses and also host–pathogen interactions. These research areas will be valuable in designing future strategies for controlling food-borne pathogens.

The diversity of the human genome leads to many functional differences between individuals. The present review focuses on genetic variations, both rare and common, that are of relevance to digestion of the sugars and starches that form a major part of human diets, and considers these in relation to the evolution of our species. For example, intolerances of dietary saccharides are not usually life-threatening because symptoms can be avoided by removal of the offending sugar from the diet, and deficiencies of the relevant enzymes are in some cases found at relatively high frequencies in certain populations. This is of evolutionary interest in relation to changes in the human diet, and the lactase-persistence polymorphism, in particular, provides an interesting model. More of the world's adult population are lactase-deficient than have high lactase. The other deficiencies are however much more rare, but the significance of variant alleles at these loci, and also heterozygosity for deficiency alleles, to human nutrition and health is an area that is relatively unexplored.

In the search for alternatives to banned in-feed antibiotics, a concept was developed based on studies with medium-chain fatty acid-containing triacylglycerols (MCTAG) and selected lipases for in situ generation of diacylglycerols, monoacylglycerols and medium-chain fatty acids (MCFA) in the stomach and proximal gut of piglets. MCFA are known to have strong antibacterial properties but can hardly be used as such because of their repellent odour and taste. Those problems could be overcome by the generation of MCFA in situ. The concept was tested in vitro and validated in vivo with gastric-cannulated piglets and under field conditions, including effects on zootechnical performance, with classical antibacterial growth promoters or organic acids acting as positive controls. Furthermore, the metabolic and dietary constraints on the nutritional and nutritive use of MCTAG and/or MCFA (for example, the effects on digestive physiology, gut flora, feed intake, performance, carcass composition) are reviewed. The role of natural preduodenal lipase activity, the presence of endogenous plant lipase activity in raw materials and the feasibility for exogenous lipase addition to the feed are discussed, in order to optimize the concept. The present review illustrates the similarity of the action of MCFA and commonly used antimicrobials on the flora (total flora, Gram-positive flora, Gram-negative flora, potential pathogens) and epithelial morphology and histology in the foregut. These observations are believed to be the basis for obtaining optimal growth performances. In addition, these naturally occurring antimicrobial agents have little or no human or animal toxicity and induce no problems of residues and cross-resistance induction. They are proposed as a valuable alternative to in-feed antibiotics, used for growth promotion, and even for the preventive and curative treatment of gastrointestinal diseases.

The metalloid Se is ubiquitous in soils, but exists mainly in insoluble forms in high-Fe, low-pH and certain leached soils, and hence is often of limited availability to plants. Consequently, it is often supplied by plants to animals and human consumers at levels too low for optimum health. Se deficiency and suboptimality are manifested in populations as increased rates of thyroid dysfunction, cancer, severe viral diseases, cardiovascular disease and various inflammatory conditions. Se deficiency probably affects at least a billion individuals. Optimal cancer protection appears to require a supra-nutritional Se intake, and involves several mechanisms, which include promotion of apoptosis and inhibition of neo-angiogenesis. Evidence suggests that in some regions Se is declining in the food chain, and new strategies to increase its intake are required. These could include education to increase consumption of higher-Se foods, individual supplementation, food fortification, supplementation of livestock, Se fertilisation of crops and plant breeding for enhanced Se accumulation. Se levels in Australian residents and wheat appear to be above the global estimated mean. Wheat is estimated to supply nearly half the Se utilised by most Australians. Increasing the Se content of wheat represents a food systems approach that would increase population intake, with consequent probable improvement in public health and large health cost savings. The strategies that show most promise to achieve this are biofortification by Se fertilisation and breeding wheat varieties that are more efficient at increasing grain Se density. Research is needed in Australia to determine the most cost-effective fertilisation methods, and to determine the extent of genetic variability for grain Se accumulation. Before recommending large-scale fortification of the food supply with Se, it will be necessary to await the results of current intervention studies with Se on cancer, HIV and AIDS, and asthma.

The demand for organic foods is constantly increasing mainly due to consumers' perception that they are healthier and safer than conventional foods. There is a need for information related to food safety to inform consumers of the health benefits and/or hazards of food products of both origins, in order to optimise the impact on health and minimise the risks. Several gaps and limitations in scientific knowledge with regard to food risk evaluation make it difficult to draw generalised conclusions. Still, some organic foods can be expected to contain fewer agrochemical residues and lower levels of nitrate than conventionally grown alternatives. On the other hand, environmental contaminants are equally present in foods of both origins. With regard to other food hazards, such as natural chemicals, microbial pathogens and mycotoxins, no clear conclusions can be drawn, although several interesting points can be highlighted. It is difficult, therefore, to weigh the risks, but what should be made clear to consumers is that ‘organic’ does not equal ‘safe’. If producers adopt proper agricultural practices and consumers maintain hygienic conditions, risks associated with food contaminants can be minimised, regardless of the food's organic or conventional origin.

During ageing, a progressive loss of muscle mass has been well described in both man and rodents. This loss of proteins results from an imbalance between protein synthesis and degradation rates. Although some authors have shown a decrease of myofibrillar protein synthesis rates in human volunteers, this imbalance is not clearly apparent when basal rates of protein turnover are measured. A decrease in muscle protein synthesis stimulation was detected nevertheless in ageing rats during the postprandial period, suggesting that the ‘meal signal’ was altered during ageing. Many results now suggest that aged muscle is less sensitive to the stimulatory effect of amino acids at physiological concentrations but is still able to respond if the increase in aminoacidaemia is sufficiently large. Indeed amino acids play an important role in regulating muscle protein turnover both in vitro and in vivo. At the molecular level, amino acids modulate gene expression. Amino acid response elements have been characterised in the promoter of transcriptional factor CCAAT-enhancer binding protein homologous protein and asparagine synthetase genes. Among amino acids, leucine seems to play the major role in regulating the metabolic function. It inhibits proteolysis and stimulates muscle protein synthesis independently of insulin. Leucine has been shown to act as a real mediator by modulating specifically the activities of intracellular kinases linked to the translation of proteins such as phosphatidylinosinol 3′ kinase and mammalian target of rapamycin–70 kDa ribosomal protein S6 (p70S6K) kinases. We recently demonstrated in vitro that protein synthesis of ageing rat muscles becomes resistant to the stimulatory effect of leucine in its physiological concentration range. However, when leucine concentration was increased greatly above its postprandial level, protein synthesis was stimulated normally. Moreover, we studied the effect of meal leucine supplementation on in vivo protein synthesis in adult and ageing rats. Leucine supplementation had no additional effect on muscle protein synthesis in adults but totally restored its stimulation in ageing rats. Whether chronic oral leucine supplementation would be beneficial for maintaining muscle protein mass in elderly men and women remains to be studied.

In the present review, the quantitative impact of dietary aflatoxin, deoxynivalenol (DON) and fumonisin concentrations on performance of pigs and broilers is evaluated, with special emphasis on low concentrations of these toxins. Also, responses in performance of pigs and broilers to these three toxins are related to their absorption and elimination kinetics. By applying simple linear regression, information from many literature sources is integrated and condensed into, for example, estimates of depression in rates of weight gain, relative to non-contaminated diets, with increasing toxin concentrations. It was estimated that with each mg/kg increase of aflatoxin in the diet, the growth rate would be depressed by 16 % for pigs and 5 % for broilers. For DON, with each mg/kg increase in the diet, the growth depression was estimated at about 8 % for pigs, while broilers showed no response to DON concentrations below 16 mg/kg. Fumonisin showed the lowest impact on growth performance; with each mg/kg increase, the depression in growth rate was estimated at 0·4 and 0·0 % for pigs and broilers, respectively. Dietary concentrations that cause a 5 % reduction in growth rate were estimated at 0·3 and 1·0 mg/kg for aflatoxin for pigs and broilers, respectively; 1·8 and 0·6 mg/kg for pure and naturally contaminated DON for pigs, respectively; 21 and 251 mg/kg for fumonisin for pigs and broilers, respectively.

Since 1953, the definition of ‘dietary fibre’ (DF) has evolved significantly following an international debate based on analytical progress, new nutritional and physiological knowledge and also private interests of the food industry. The overall tendency is towards an extension of the definition by including resistant starches as well as non-digestible oligosaccharides. This broadened definition is indeed based on physiological considerations as these compounds are not digested in the small intestine and become substrates for the colonic microflora, resulting in fermentation products that have a variety of local and possibly also systemic effects. A main reluctance to use this definition, however, is linked to the difficulty to quantify, with a universal method, the various compounds that fulfil the characteristics defined by this broad definition. At this point, if such a definition were adopted, there are two options, not necessarily antagonistic, which would be (1) to sum the content of NSP, resistant starches and non-digestible oligosaccharides quantified by distinct methods or (2) to use the Association of Official Analytical Chemists (AOAC) method of DF analysis (AOAC 985.29, 991.43) with complementary analyses of the different non-digestible oligosaccharides likely to be present in the food. With none of these solutions being fully satisfying from a scientific but also from a practical point of view, an innovative method has to be proposed within the next decade. The present review describes the various types of DF, effects of DF consumption on physiology and metabolism, past and current definitions, analytical aspects to measure DF and some aspects of DF claims and food labelling.

The Japanese scientific academic community defined ‘functional food’ early in the 1980s. That is, functional foods are those that have three functions. The primary function is nutrition. The secondary function is a sensory function or sensory satisfaction. The third is the tertiary function, which is physiological. The Japanese Ministry of Health, Labour, and Welfare (MHLW) set up ‘Foods for Specified Health Use’ (FOSHU) in 1991 as a regulatory system to approve the statements made on food labels concerning the effect of the food on the human body. Food products applying for approval by FOSHU are scientifically evaluated in terms of their effectiveness and safety by the Council of Pharmaceutical Affairs and Food Hygiene under the MHLW. The regulatory range of FOSHU was broadened in 2001 to accept the forms of capsules and tablets in addition to those of conventional foods. FOSHU increased the total to about 330 items in January 2003. The MHLW enacted a new regulatory system, ‘Foods with Health Claims’, in April 2001, which consists of the existing FOSHU system and the newly established ‘Foods with Nutrient Function Claims’ (FNFC). Under the FNFC, twelve vitamins (vitamins A, B1, B2, B6, B12, C, E, D, biotin, pantothenic acid, folic acid, and niacin) and two minerals (Ca and Fe) are standardized. Examples of claims regarding these substances are as follows: ‘Calcium is a nutrient which is necessary to form bones and teeth’; ‘Vitamin D is a nutrient which promotes calcium absorption in the gut intestine and aids in the formation of bones.’ The upper and lower levels of the daily consumption of these nutrients are also determined. The labelling of functional foods should always be based on scientific evidence and be in harmony with international standards. The nutrient–function claim was adopted in the guidelines for nutrition claims by the Codex Alimentarius in 1997. The claims of the Japanese FNFC are equivalent to the nutrient function claims standardized by the Codex Alimentarius. The enhanced function claim and the disease risk-reduction claims were proposed by both the Codex Alimentarius and an Economic Union project in 1999. The structure function claim, which is similar to the enhanced function claim, was enacted by the Dietary Supplement Health and Education Act in the USA in 1994. Most of the statements of the Japanese FOSHU system are close to the category of structure/function claims in the USA or the enhanced function claims of the Codex Alimentarius.

Poly(ADP-ribose) synthetase/polymerase (PARP) activation causes NAD+ depletion in pancreatic β-cells, which results in necrotic cell death. On the other hand, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (CD38) synthesizes cyclic ADP-ribose from NAD+, which acts as a second messenger, mobilizing intracellular Ca2+ for insulin secretion in response to glucose in β-cells. PARP also acts as a regenerating gene (Reg) transcription factor to induce β-cell regeneration. This provides the new concept that NAD+ metabolism can control the cellular function through gene expression. Clinically, PARP could be one of the most important therapeutic targets; PARP inhibitors prevent cell death, maintain the formation of a second messenger, cyclic ADP-ribose, to achieve cell function, and keep PARP functional as a transcription factor for cell regeneration.

Leptin is a 16 kDa protein synthesized and secreted primarily from adipocytes. Leptin acts centrally to regulate appetite and energy expenditure and has peripheral effects to coordinate whole-body energy metabolism. Leptin acts as an energy balance and nutrient sensor; its expression and function are regulated by endocrine and dietary factors. Leptin regulates lipid metabolism, specifically lipid storage in adipocytes as well as in skeletal muscle, liver and the pancreas. Effects of leptin on tissue lipid metabolism include regulation of lipogenesis and fatty acid oxidation. Leptin resistance is a hallmark of rodent and human obesity and appears to be due to defects in leptin-receptor signalling (proximal and perhaps distal) as well as impaired leptin transport into the brain. Dietary composition, especially dietary fatty acid intake and profile, impacts on the expression of genes encoding leptin and leptin receptors as well as downstream leptin effectors. Dietary fat consumption, especially consumption of saturated fatty acids, can induce leptin resistance. Leptin has been implicated in nutritional programming during fetal and neonatal growth with long-term effects on susceptibility to obesity, diabetes and CHD in adults.

Exercise causes a dramatic increase in energy requirements because of the metabolic needs of working muscles. Exercise-dependent factors regulate fuel use. Absolute exercise intensity determines the exercise-induced increase in energy demands, whereas exercise intensity relative to an individual's maximal aerobic capacity (VO2max) determines the proportional contribution of different fuel sources (i.e. plasma glucose, plasma fatty acids, muscle glycogen and intramuscular triacylglycerols). Endurance training increases aerobic capacity in muscle and the oxidation of fat during exercise. In addition, exercise-independent factors, such as diet composition, sex, age, and body composition also influence substrate use during exercise. The present review discusses the regulation of substrate use during exercise in human subjects, with a focus on the role of exercise-independent factors.

Insulin resistance leads to the inability of insulin to control the utilization and storage of glucose. It is associated initially with elevated levels of circulating insulin followed by glucose intolerance which may progress to type 2 diabetes, hyperlipidaemia, hypertension, obesity and cardiovascular diseases. While the causes of these diseases are multifactorial, one nutrient that is associated with all of these abnormalities is Cr. In the presence of Cr, in a biologically active form, much lower levels of insulin are required. Modern diets, which are often high in refined carbohydrates, are not only low in Cr, but lead to enhanced Cr losses. In response to the consumption of refined carbohydrates, there is a rapid rise in blood sugar leading to elevations in insulin that cause a mobilization of Cr. Once mobilized, Cr is not reabsorbed but lost via the urine leading to decreased Cr stores. Several studies involving both human subjects and experimental animals have reported improvements in insulin sensitivity, blood glucose, insulin, lipids, haemoglobin A1c, lean body mass and related variables in response to improved Cr nutrition. However, not all studies have reported beneficial effects associated with improved Cr nutrition. Well–controlled human studies are needed to document an unequivocal effect of Cr on insulin sensitivity in human subjects. Studies need to involve a significant number of subjects with insulin resistance, glucose intolerance or early stages of diabetes, who have not been taking supplements containing Cr for at least 4 months, and involve at least 400 to 600 μg supplemental Cr daily or more. Studies should be at least 4 months to document sustained effects of supplemental Cr on insulin resistance and related variables. Cr is a nutrient and not a therapeutic agent and therefore will only be of benefit to those whose problems are due to suboptimal intake of Cr.

The link between genome instability and adverse health outcomes during the various stages of life, such as infertility, fetal development and cancer, is briefly reviewed against a background of evidence indicating that genome instability, in the absence of overt exposure to genotoxins, is itself a sensitive marker of nutritional deficiency. The latter is illustrated with cross-sectional and dietary intervention data obtained using the micronucleus assay, an efficient biomarker for diagnosing genome instability and nutritional deficiency. The concept of recommended dietary allowances for genome stability and how this could be achieved is discussed together with the emerging field of nutritional genomics for genome stability. The review concludes with a vision for a disease-prevention strategy based on the diagnosis and nutritional treatment of genome instability, i.e. ‘Genome Health Clinics’.

Thiamin plays a key role in the maintenance of brain function. Thiamin diphosphate is cofactor for several enzymes involved in glucose metabolism whereas thiamin triphosphate has distinct properties at the neuronal membrane. Thiamin metabolism in the brain is compartmented between neurons and neighbouring glial cells. Thiamin deficiency is commonly encountered in severe malnutrition associated with chronic alcoholism, HIV–AIDS and gastrointestinal disease where it frequently results in Wernicke's encephalopathy (the Wernicke–Korsakoff syndrome). Wernicke's encephalopathy is severely underdiagnosed according to clinical criteria in both alcoholic and HIV–AIDS patients. Magnetic resonance imaging reveals bilateral ventricular enlargement, mammillary body atrophy and cerebellar degeneration indicative of selective neuronal loss that is characteristic of Wernicke's encephalopathy. Several mechanisms have been proposed to explain this selective loss of neurons including a cerebral energy deficit resulting from reductions in activity of thiamin diphosphate-dependent enzymes, oxidative stress and N-methyl-D-aspartate receptor-mediated excitotoxicity. Both microglia and perivascular endothelial cells are sources of NO and oxidative stress in thiamin deficiency. Decreased activities of thiamin diphosphate-dependent enzymes (in particular α-ketoglutarate dehydrogenase) have also been reported in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases independent of patient malnutrition. In these cases, decreased activities result from direct toxic actions of oxidative stress and β-amyloid produced as part of the neuronal cell death cascade in these disorders.