title: The Alzheimer pandemic: is paracetamol to blame?
abstract: BACKGROUND
  The clinical recognition of a form of dementia closely resembling Alzheimer's disease dates from around 1800. The role of analgesics derived from coal-tar in the spread of the pandemic is traced in terms of the introduction of phenacetin (PN) in 1887; its nephrotoxicity; the observation of lesions characteristic of the disease by Fischer and Alzheimer; the discovery of paracetamol (PA) as the major metabolite of PN; the linking of kidney injury and dementia with high PN usage; and the failure of PN replacement by PA to halt and reverse the exponential, inexorable rise in the incidence of Alzheimer-type dementia. Fischer observed his first case before Alzheimer; it is proposed to rename the syndrome Fischer-Alzheimer disease (F-AD). Disease development: PA-metabolising enzymes are localised in the synaptic areas of the frontal cortex and hippocampus, where F-AD lesions arise. The initiating chemical lesions in liver poisoning comprise covalent binding of a highly reactive product of PA metabolism to proteins; similar events are believed to occur in brain, where alterations in the antigenic profiles of cerebral proteins activate the microglia. β-Amyloid forms, and, like PA itself, induces nitric oxide synthase. Peroxynitrite modifies cerebral proteins by nitrating tyrosine residues, further challenging the microglia and exacerbating the amyloid cascade. Spontaneous reinnervation, N-acetyl cysteine administration and tyrosine supplementation may attenuate the early stages of F-AD development.
  
  
  CONCLUSIONS
  F-AD is primarily a man-made condition with PA as its principal risk factor.
authors.affiliation: 30 Poplar Walk, London SE24 0BU, UK. darkshad@hotmail.co.uk.
authors.forename: Günther Robert Norman
authors.initials: GR
authors.lastname: Jones
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology / Q000266:history; D016564:Amyloid beta-Protein Precursor / Q000276:immunology / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D050216:Metabolic Detoxication, Phase I / Q000502:physiology; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D058873:Pandemics; D030421:Peroxynitrous Acid / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D018712:Analgesics, Non-Narcotic; D001324:Autoantigens; D030421:Peroxynitrous Acid; D000082:Acetaminophen