Aluminum and Dr. Bredesen's 3 Types of Alzheimer's

I have a facebook group Alzheimer's: Late and Early Onset, APOE4 https://www.facebook.com/groups/509038829797535/

In an Alzheimer's forum I was asked what my husband thought of Dr. Bredesen's 3 Types of Alzheimer's.   Here is a response from my husband Dennis N Crouse who is a chemist and has been reading the scientific literature for the past several years in order to help his mother who has Alzheimer’s.  

 “I agree with Dr. Bredesen on his 3 types of Alzheimer’s.  The 3 types are actually three phases of Alzheimer’s all caused by aluminum accumulation. 

Type 1 inflammatory – There are at least 11 metals that create reactive oxygen species (ROS) in your brain. However aluminum creates significantly more ROS in the glial cells of the human brain than any of the other 10 metals. Because of this, aluminum is a physiological stressor that causes inflammation of the brain. Dr. Bredesen claims that inflammation causes a rise in your tumor necrosis factor (TNF).  There is another perspective: aluminum has been shown to epigenetically cause a rise in TNF and this in turn decreases gene expression for methionine synthase required to lower homocysteine levels.

Tsunoda, M. and Sharma, R.P,; Modulation of tumor necrosis factor alpha expression in mouse brain after exposure to aluminum in drinking water; Arch. Toxicol.; Nov.; 73(8-9):419-26 (1999)

https://www.ncbi.nlm.nih.gov/pubmed/10650912

 Type 2 – Dr. Bredesen’s Type 2 is actually part of the biochemical fingerprint of aluminum accumulation.  Dr. Bredesen mentions that lower than normal levels of active vitamin D and higher than normal levels of homocysteine are usually the biochemical fingerprint of his Type 2 Alzheimer’s.  Aluminum inhibits active vitamin D biosynthesis lowering levels of active vitamin D. Also aluminum inhibits the methylation of homocysteine resulting in an increase of homocysteine in blood plasma. Aluminum does this by both inhibiting the expression of methionine synthase and the activation of this enzyme.

Waly, M., et al.; Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal; Mol. Psychiatry 9, 358-70 (2004)

https://www.ncbi.nlm.nih.gov/pubmed/14745455

Waly, M. I-A., and Deth, R.; Neurodevelopmental toxins deplete glutathione and inhibit folate and vitamin B12-dependent methionine synthase activity – a link between oxidative stress and autism; FASEB J; 22:894 1 (2008)

http://www.fasebj.org/content/22/1_Supplement/894.1

 Type 3 – Aluminum is neurotoxic and it kills neurons, inhibits neurite growth, and synapse development.  It also interferes with calcium, as an internal messenger inside neurons, by modifying calmodulin’s calcium receptor site.   People with the APOE4 gene produce more beta amyloid which forms neurotoxic oligomers that react with aluminum to form neurotoxic droplets (Nano droplets) of amyloid oligomers.  These neurotoxic droplets are very stable and mobile in the brain and are “freezing” the amyloid in the oligomeric state.  These beta amyloid oligomers are 10 times more neurotoxic than amyloid plaque.”  Dennis N Crouse  PhD

Drago, D., et al.; Potential pathogenic role of β-amyloid_1-42-aluminum complex in Alzheimer’s disease; Int. J. Biochem. & Cell Biol.; 40:731-46 (2008)

http://europepmc.org/abstract/med/18060826

Denise Drago -  Aluminum Modulates Effects of βAmyloid_1–42 on Neuronal Calcium Homeostasis and Mitochondria Functioning and Is Altered in a Triple Transgenic Mouse Model of Alzheimer's Disease  2008

http://online.liebertpub.com/doi/abs/10.1089/rej.2008.0761