Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Soluble Toxic Cause of AD
- John Fryer (11 May 2001)
-
Alzheimer's pathogenesis: tau and amyloid - a consensus or a challenge for a third party quest?
- Alexei R Koudinov, Natalia V Koudinova (4 September 2001)
|
|
|||
|
John Fryer, Retired Scientist
Send response to journal:
|
Scott Gottlieb has made an important contribution to our knowledge of AD. The soluble toxic chemical idea and the toxic protein idea should be vigourously explored. Much work on not the Amyloid peptides/protein but the Tau protein shows that organophosphorus molecules attach to the protein molecule and cause it to lose its shape - ie tangle. Removal of the organophosphorus from the protein causes it to assume its original shape. At least 5 molecules of OP are needed to deform the protein. What is not clear from the research is the source of this "rogue" OP. If we hazard a guess that AD has risen from a rare disease to very common in tandem with the use of OP molecules for insecticidal use and assume that far from being environmentally friendly that they are persistant as was and is the case for DDT and other Organochlorine (OC) molecules - we are probably all harbouring circa 12 ppm of OP pesticide residues. Enough to cause the fatal degeneration of our nerves in our brains by the age of 80 should we live that long. The standard preparation of microbiological slides will of course lose the soluble and offending OP molecules. Hence the reason possibly for the strange appearance of vacuoles in certain slides of nervous degenerative illness? We need to be a little cleverer in our search for the cause of AD and Scott Gottlieb has made an important step in this search for the cause of what surely is an environmental illness? My candidate molecule for harm is Diethyl Phosphate a break down product from ethyl phosphate insecticides such as Diazinon much used from Jan 1st 1985 for sheep dipping twice a year and in my opinion a contributory factor in the BSE illness. Most BSE cattle were on sheep pastures or had other OP contact eg from intervention wheat OP treated to the point where it was passed as unfit for human but fit for cattle consumption. This chemical (diazinon) was suspended from use for such purpose on Jan 1st 2000 and on December 5th 2000 the chemical was withdrawn from use worldwide over a period of the next four years by agreement with the manufacturer and the CDC in USA. There are other many very simple breakdown products from OP insecticides and the work and research on them is skimpy - believed to be harmless breakdown products and not the candidate molecules for causation of AD. Is this the cause of AD or is it just another blind alley? We need to find for sure what chemicals will phosphorylate the tau protein and there are many to consider from OP insecticides and their metabolites. The OP toxic molecules do occur naturally in nature and provide a pathway for the natural production of rogue protein as is found in a few places worldwide, notably in Guam for example. John Fryer |
|||
|
|
|||
|
Alexei R Koudinov, senior research scientist Berezov Academic Lab., Rus Acad Med Sci, and Weizmann Inst., Biol. Regulation, Rehovot 76100 Israel, Natalia V Koudinova
Send response to journal:
|
To add to the discussion on Alzheimer's pathogenesis (see BMJ 2001; 322: 1085 News Roundup) we would like to attract readers attention to very recent Science magazine commentary article "Tauists and baptists United - Well Almost" accompanying two studies by Lewis et. al. and Gotz et.al., assaying possible pathologic relation between amyloid beta protein and tau. We would like to point out that some neurodegenerative diseases, characterized by both tau tangles and amyloid beta deposition, represent neuronal cholesterol pathologies, the primary example being Niemann-Pick type C disease [ 1 ]. Faulty brain cholesterol dynamics is a minimal requirement causing both tau and amyloid beta neurochemistry change in genetically naive lab animals, brain slices and cell cultures (see [ 1, 2 ] for details). As it was proposed [ 3 ], experimentally addressed and discussed [ 1 ], the change in both tau and amyloid beta protein neurochemistry may independently help to recover synaptic function and plasticity, the prime neurodegeneration aim, impaired by neuronal cholesterol turnover misregulation [ 1, 4 ]. In our view both understanding brain cholesterol dynamics associated with learning, memory and cholesterol-lowering medicine (see BMJ 2000; 321: 1241 ), and proposed in Science commentary the study of transgenic mouse models containing amyloid and tau pathologies, have legacy to contribute to further elucidation tau-amyloid pathophysiological relation and primacy. References: 1. Koudinov AR, Koudinova NV. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. published June 27, 2001, 10.1096/fj.00-0815fje [ PubMed Citation ] [ Abstract and Full text at FASEB J ] [ Authors WEB site ] [ Authors WEB site mirror ] [ Authors related BMJ Electronic Response ]. 2. Fan QW, Yu W, Senda T, Yanagisawa K, and Michikawa, M. (2001) Cholesterol-dependent modulation of tau phosphorylation in cultured neurons. J. Neurochem. 76, 391-400 [ PubMed citation ] [ Abstract and Full Text at J Neurochem ] 3. Mesulam MM. (1999) Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles. Neuron. 24, 521-529. [ PubMed citation ] [ Full Text at Neuron ]. 4. Matthies H, Schulz S, Hollt V, and Krug M. (1997) Inhibition by compactin demonstrates a requirement of isoprenoid metabolism for long-term potentiation in rat hippocampal slices. Neurosci.79, 341-346 [ PubMed citation ] [ Abstract and Full Text at Neuroscience ]. |
|||