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Similarities between autism and Alzheimer's disease
Lane Simonian
Posted: Tuesday, October 23, 2012 8:35 PM
Joined: 12/12/2011
Posts: 4854


This is an interesting article noting that mercury and various infections may contribute to the formation of amyloid plaques and each may play a role at times in both autism as well as Alzheimer's disease.   

 

http://www.ageofautism.com/2012/10/what-is-causing-beta-amyloid-production-in-alzheimers-and-autism.html 

 

Because I have some limited ties to autism,  I am interested in the connection between the two disease.  Here is another possible one: 

 

Another potential therapeutic target is peroxynitrite. Agonists of NMDA receptors increase concentration of calcium leads to nitric oxide (NO) synthesis. NO reacts with free radical superoxide and produces the powerful oxidant peroxynitrite. Nitric oxide and peroxynitrite may cause glutamate release and neuronal death (Brown and Neher), and peroxynitrite is toxic for mitochondrial activity and DNA (Spencer, Wong et al. 1996). The hyperglutaminergic condition in ASD, the role of glutamate in production of inflammation (which is elevated in ASD; Blaylock and Strunecka, 2009), and peroxynitrite, toxicity of peroxynitrite for DNA, and the prevention of neuronal loss by scavengers of peroxynitrite in co-cultured neurons (Mander and Brown 2005) all point to peroxynitrite as a novel potential treatment target for autism.

 

Peroxynitrite decomposition catalysts block nitration of glutamate transporters, especially GLT1 and glutamine synthetase (Chen, Muscoli et al.). These two proteins have key roles in transmission of glutamate into the intracellular space. Inhibition of GLT1 and glutamine synthetase by peroxynitrite increases glutamate level and causes neurotoxicity. Therefore, therapeutic approaches intelligently targeting peroxynitrite in brain could be worthwhile to be further studied in preclinical experimental trials for management of ASD.

 

http://www.jneurosci.org/content/30/15/5346/reply 

 

Why then is autism not Alzheimer's disease.  One possible explanation is that individuals with autism cannot breakdown polyphenols and polyphenols provide some protection against the damage caused by peroxynitrites.  So many of the problems of Alzheimer's disease, including sleep disorders, lack of social recognition, and the progressive loss of short-term memory are not as marked as in autism except in severe cases.  On the other because they cannot breakdown polyphenols, autistic individuals often have problems with anxiety and other behavioral issues similar to a person with Alzheimer's disease with high levels of adrenaline.  Thus again the challenge of finding the right combination of compounds to improve cognition while not increasing agitation.   

 

 

 


Serenoa
Posted: Tuesday, November 13, 2012 1:17 PM
Joined: 4/24/2012
Posts: 484


This is a fascinating connection that I hadn't thought of before! Thanks Lane! Here we have evidence that antibiotics, bacteria and possibly Mercury are involved with Autism, and that abnormal amounts of Beta Amyloid or its precursor APP are present in Autism.    

  

Here is the evidence: 

 

2006. “Children with ASD [Autism Spectrum Disorder] were found to have significantly more ear infections than the typically developing children as well as to use significantly more antibiotics. Typically developing children had significantly more illness-related fevers.”

http://journals.lww.com/jrnldbp/Abstract/2006/04002/Early_Medical_History_of_Children_with_Autism.10.aspx 

 

2007. “Children with autism had significantly (2.1-fold) higher levels of mercury but similar levels of lead and similar levels of zinc. Children with autism also had significantly higher usage of oral antibiotics during their first 12 mo of life, and possibly higher usage of oral antibiotics during their first 36 mo of life.” “Antibiotic use is known to almost completely inhibit excretion of mercury in rats due to alteration of gut flora.” “Higher usage of oral antibiotics in infancy may also partially explain the high incidence of chronic gastrointestinal problems in individuals with autism.”

http://www.tandfonline.com/doi/abs/10.1080/15287390601172080 

 

2012. “This shows that penicillins and cephalosporins, as well as clindamycin, have a major impact on the normal bowel flora and therefore might well predispose subjects to overgrowth of such organisms as Clostridium difficile, and of particular importance for autism, to Desulfovibrio.”

http://www.sciencedirect.com/science/article/pii/S1075996411002423 

 

2011. “Brain neurons in cortex and cerebellar cortex and dentate nucleus in autism in the post-developmental period of life accumulate intracellular N-terminally truncated Aβ42. This may result from excessive processing of APP in the non-amyloidogenic pathway or defective degradation of N-terminally truncated Aβ42.”

 https://imfar.confex.com/imfar/2011/webprogram/Paper9407.html  

 

  I am trying to understand what the primary causal factor(s) is in AD. It may very well be something similar to what induces Autism.  Autism and AD are both age-related disorders. What if we have similar causes for both but there is only a susceptibility to these factors when very young (Autism) or old (AD). The body may deal with these detrimental factors differently depending on age.  

 

For example, metal toxicity (Mercury is mentioned in Autism) makes sense because we know that it severely impacts a developing brain, but we also know that with age, people may naturally have reduced ability to regulate homeostasis of many metals or essential elements. Therefor it may be Copper that is the toxic metal in AD.  

 

Antibiotic use may inhibit the the development of the immune system in Autism.  Can an underused immune system play a part in AD too? From the 2006 study above: “Typically developing children [i.e. normal kids] had significantly more illness-related fevers.”  We know the immune system is key in preventing AD. Several immune system treatments have been effective to some degree: vaccine, IgIV, Leukine. We also know that other problems are linked to an underdeveloped immune system like Asthma. Can we equate the rise in AD over the last century in developed countries with the lack of "illness-related fevers?" We now get vaccines for many things, we get antibiotics on demand, and most of us live in a comparatively sterile environment (with exception of schools, mass transit, etc.). 

 

The presents, absence and abnormal composition of bacteria in the gut or in the brain seems to be a factor in both diseases. Here we have a potential primary cause for the production of Amyloid in neurons. As Lane pointed out in one study, bacteria can cause upregulation of Phospholipase C (PLC) which leads to AB and peroxynitrite production. And, AB was shown to have antimicrobial properties (see Lane's previous link in this string) which may actually be helping to counteract these microbial infections or imbalances.

 

And could it be that once infection or imbalance in gut bacteria becomes chronic, as may be the case in AD, antibiotics actually help? There is evidence for antibiotics as a treatment for both Autism and AD. However, the benefits seem to disappear when treatment is discontinued in both diseases (see 2012 study above and "Brushing Teeth May Reduce Alzheimer's" post). Perhaps this is also a connection with diet as a regulator of healthy gut flora. This would also tie in with an increase in AD in developed countries and urban areas.

 

 What I would like to get at is a primary cause. I have learned much through this forum about the pathways of AD: PLC, PKC, Peroxynitrites, etc. and I agree with the evidence that phenolic compounds in essential oils can help manage and prevent the damage. What could be the primary initiator of these damaging pathways apart from genetic predisposition. What is the environmental cause or causes, whether they be microbs, toxic metals, improper nutrition? 

 

 I think this is a very exciting connection and that there are some great clues with these Autism similarities. Does this resonate with anyone? Can anyone make sense of this evidence? Thanks for any comments, everything helps.

 

 


Lane Simonian
Posted: Tuesday, November 13, 2012 6:14 PM
Joined: 12/12/2011
Posts: 4854


You are helping me put more things together, Serenoa.  I did not know that antibiotics inhibit the excretion of mercury, for example.  This may explain a large part of why they are deleterious for people with autism. 

 

Glutathione is critical for the removal of mercury,  In autistic childern and adults a genetic defect reduces the production of glutathione.  In Alzheimer's disease, peroxynitrites help to deplete glutathione.  Mercury in vaccines, now predominantly flu shots, and dental amagams perhaps in combination with mercury in the air and water may trigger autism and Alzheimer's disease in some cases as mercury activates phospholipase C, contributing both to the production of amyloid plaques and peroxynitrites. 

 

http://www.ncbi.nlm.nih.gov/pubmed/2260972 

 

Interesting, too, because Protein kinase C is said to produce more of the supposedely non-toxic version of the amyloid precursor protein (the n-terminal fragment rather than the c-terminal). 

 

https://docs.google.com/viewer?a=v&q=cache:-406BZ3e_24J973.ccmu.edu.cn/DOC/thesis/20071126110227.pdf+protein+kinase+C+n-terminal+amyloid+precursor+protein&hl=en&gl=us&pid=bl&srcid=ADGEESgiG6Xqqe9ISkPTPUWhSDBDl3y4LwppgstFPRCuDKkS86zn4ObJRmseJiNlI53XMpV6xzKx8AB5y84Vdu2nCEPp1_WD8o6fZ2YiI7bIRXPNabX733G5gKB3cEpt0ssyMsTtfTKd&sig=AHIEtbSSfNCgOOp9DOlr8oEsxwrJSsXt4w 

 

Indeed, some scientists working or citing research such as the above, have suggested protein kinase C activation as a means to prevent Alzheimer's disease (bad idea).  The long-term effect of protein kinase C activation and calcium release is to increase the production of amyloid plaques.  Indeed, in the case of autism, the more severe the form and the longer the number of years, the more amyloid plaque that is produced. 

 

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035414 

 

Ironically, the manner in which amyloid plaques may protect against bacteria is through the increased production of peroxynitrites. 

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898335/ 

 

So great, the peroxynitrites help to protect against bacteria, but also kill brain cells.   

 

I have a long list of things that increase the formation of amyloid plaques and peroxynitrites (some more certain than others).  They include chronic bacterial and viral infections, high glucose levels, high blood pressure due to high sodium levels, Down syndrome, Angiotensin II (a risk factor for high blood pressure), bisphosphonate osteoporosis drugs (Fosamax, Boniva, and Actonel), mercury, aluminium fluoride, copper, organophosphate pesticides, nitric oxide in air pollution, nitrites and nitrates in processed meats, late estrogen replacement therapy, and stress.  And those are just the ones that I know of (or think I know of).  No wonder so many people end up with this disease.  But if you find the right peroxynitrite scavenger you can treat the disease (and perhaps autism as well).    

 

 


Serenoa
Posted: Tuesday, November 13, 2012 7:35 PM
Joined: 4/24/2012
Posts: 484


 Thanks Lane. Great information! Lots to think about.

 
  "I have a long list of things that increase the formation of amyloid plaques and peroxynitrites (some more certain than others).  They include chronic bacterial and viral infections, stress, high blood pressure, high glucose levels, high blood pressure due to high sodium levels, Down syndrome, Angiotensin II (a risk factor for high blood pressure), bisphosphonate osteoporosis drugs (Fosamax, Boniva, and Actonel), mercury, aluminium fluoride, copper, organophosphate pesticides, nitric oxide in air pollution, nitrites and nitrates in processed meats, late estrogen replacement therapy, and stress.  And those are just the ones that I know of (or think I know of).  No wonder so many people end up with this disease.  But if you find the right peroxynitrite scavenger you can treat the disease (and perhaps autism as well)."

 

My mother was on a bisphosphonate drug about a year or two before we noticed AD symptoms. They also caused bone spurs in her feet and Calcium deposits in her breast, she discontinued them after a year or so. She had a pretty high-stress job but no stress for several years before symptoms showed up (after she retired). She hardly ever gets sick, always refused vaccines, very good immune system. With one possible exception, a violent stomach bug she picked up in Europe probably 10 years before AD symtoms. She had lingering effects from this (I just realized this!). Other than that nothing out of the ordinary as far as bad diet, toxic metal exposure, high blood pressure, etc.  

 

Onward, you had asked if we tried anything besides Leukine, and if it helped. I recently got her on a high quality cinnamon pill twice a day approved by her doctor. She was on it for about six months and we saw no benefit. She is currently on Stresstabs/Zinc prescribed by her doctor. No noticeable difference.

 

 

  


onward
Posted: Tuesday, November 13, 2012 8:24 PM
Joined: 12/20/2011
Posts: 217


Serenoa wrote:

  ... Onward, you had asked if we tried anything besides Leukine, and if it helped. I recently got her on a high quality cinnamon pill twice a day approved by her doctor. She was on it for about six months and we saw no benefit. She is currently on Stresstabs/Zinc prescribed by her doctor. No noticeable difference.

 

 

   


Thanks, Serenoa.  I appreciate the info that you and Lane have shared in this thread.