Neurons and Exercise

Neurons and Exercise

Wednesday, September 7, 2016

Introduction to the blog


Welcome to my blog. This blog introduces you to the culprit responsible for Alzheimer’s, autism, and stroke.  This monster lurks in our food, drinking water, pharmaceuticals, and brains.  This blog also introduces you to 7 supplements, 7 lifestyle choices, and one dissolved mineral which work together to prevent the monster from causing Alzheimer’s, autism, and stroke in your brain and the brains of those you love. 

My interest in dementia started after an acquaintance died of the after-effects of a stroke and my mother and a friend’s mother, both 86 years old, began suffering severe frustration and panic attacks due to short term memory failure.  Having no preconceived notions about dementia and autism, I spent a number of years reading research articles in scientific journals. The search for the causes of Alzheimer’s, autism, and stroke started as a mystery and once solved it transformed into a crusade to rid my life of an evil monster.  I found this monster lurking in my medicine cabinet, food pantries, refrigerator, and the water pipes leading into my home.   This monster has been damaging the brains of newborn infants, elderly family members, and everyone in between for years.  It has remained undetected because of our lack of information and false reassurances by those in positions of responsibility who we have trusted with our health. It is time to take on this monster as both individuals and as a culture.  Wake up, read this blog and my book, and become informed before this monster claims your brain and the brains of those you love. I had not originally planned to write a blog or a book but once the monster was unveiled, I had no other choice. 

The close relationship of Alzheimer’s disease (AD) to autism, and stoke will be discussed.  These diseases are modern mismatch diseases created by our carefully evolved brains attempting to function in the presence of a chemical monster not experienced during the brain’s evolution.

The underlying goal of this blog is to create a cultural change in the way we view Alzheimer’s, autism, and stroke.  This blog encourages preventative measures to be taken by you and your family. It also encourages cultural changes on a larger scale than your family. For these changes to take place we need more people all wanting the same changes. So please tell family and friends about this blog. 

My book, Prevent Alzheimer's Autism and Stroke with 7 Supplements, 7 Lifestyle Choices and a Dissolved Mineral, is available on Amazon in print and kindle.  

Introduction to my book Prevent Alzheimer's, autisim and stroke with 7 Supplements, 7 Lifestyle Choices, and a Dissolved Mineral

 Here is a link to my book

My wife Laurie Adamson has a facebook group  Alzheimer's: Late and Early Onset, APOE4


I have found a surprising connection between Alzheimer’s, autism, and stroke and this ground-breaking book describes their common causal factor.  These diseases are modern mismatch diseases created by our brains attempting to function in the presence of a chemical monster at levels not experienced during the brain’s evolution. This book describes specific preventative measures to be taken by you and your family to rid yourself of this chemical monster. It also encourages cultural changes that will allow our society to prevent these mismatch diseases. Most importantly a preventative system for individuals is described in this book involving 7 specific supplements, 7 lifestyle choices, and a dissolved mineral that will prevent Alzheimer’s, autism, and stroke.  This is also a combination therapy that has been shown to reverse the cognitive decline seen in early-stage Alzheimer’s disease.  Elements of this combination therapy have also been found to reverse the course of autism in the very young and the course of hardening of the arteries and stroke in the very old.
My interest in dementia started after an acquaintance died of the after-effects of a stroke and my mother and a friend’s mother, both 86 years old at the time, began suffering severe frustration and panic attacks due to short term memory failure.  Having no preconceived notions about dementia and autism, I spent a number of years reading research articles in scientific journals. The search for the causes of Alzheimer’s and stroke started as a mystery and led to a surprising connection with the cause of autism. Once the mystery was solved it transformed into a crusade.  I found this monster lurking in my medicine cabinet, food pantries, refrigerator, and the water pipes leading into my home.   This monster has been damaging the brains of newborn infants, elderly family members, and everyone in between for years.  It is time to take on this monster as both individuals and as a culture. Reading the book will allow you to make an informed decision about what recommendations you will use to prevent this monster from claiming your brain and the brains of those you love.

Being a biochemist I am naturally suspicious of supplementing my diet with impure herbal extracts.  Small traces of toxic impurities in these extracts can do damage to your body and especially your brain.  Therefore this book only recommends supplements containing purified biochemicals and a dissolved mineral all of which are commonly found in your body.
The Alzheimer’s Association finds that Alzheimer’s disease is grossly misunderstood and underestimated.  When they surveyed people in 12 countries they found: 
 “59 percent of people surveyed incorrectly believe that Alzheimer's disease is a typical part of ageing and 40 percent of people believe that Alzheimer's is not fatal”.

Alzheimer’s (AD) is a currently a terminal disease but it is not an inevitable part of aging.  The following table will give you some “food” for thought.  Does this table suggest that AD is a typical part of ageing? 

There are countries in the world, such as Malaysia and Singapore, where people with similar life expectancy to the U.S. have much less AD.   This book explains why AD is not prevalent in some parts of the world and how countries like the U.S. can lower their rate of AD.  This book also explains how individuals can take steps to lower their risk of AD and work toward cultural changes in their countries to lower the rate of AD. True prevention is only possible by first discovering the cause of a disease such as Alzheimer’s. The book begins as I did, searching for the cause of Alzheimer’s.  I hope you join me in this exciting search by reading Chapter 1.

Monday, September 5, 2016

Chapter 1 Conclusion - Prevalence, Symptoms, Diagnosis of AD

Prevalence of Alzheimer’s Disease

The 2002 ADAMS study of dementia in the U.S. estimated that 2.7 million people in the U.S. had Alzheimer’s disease (AD)11 and by the year 2005, 24 million people worldwide had AD67.   AD prevalence is the highest in those 80 years of age and older. In 2002 there were 9 million people in the U.S. who are 80 years of age or older10. Therefore in 2002 approximately one in three people 80 years of age or older had AD.  This means almost everyone over 80 will be impacted by AD as they age.  Those of us who live to 80 and beyond will have at least a 1 in 3 chance of getting AD and, if we don’t get AD, we have at least a 1 in 2 chance of caring for a friend or relative with AD.  
The prevalence of AD is increasing both as the size of the population in the U.S. over age 65 continues to increase and as our exposure to aluminum continues to increase.  Currently the Alzheimer’s Association estimates that 5.3 million people in the U.S. have AD4.  By 2025 the number of people 65 and older with AD is estimated to reach 7.1 million and by 2050 this number is projected to be 13.8 million, barring adoption of preventive measures, such as those described in this book, or the development of medical cures. 

Symptoms of Alzheimer’s Disease

The clinical symptoms that characterize AD are:

·         Mitochondrial disease
·         Decreasing Aβ peptides and Aβ oligomers in cerebrospinal fluid
·         Increasing tau in the cerebrospinal fluid
·         Shrinkage of the brain
·         Olfactory dysfunction*
*Olfactory dysfunction or anosmia (i.e. the inability to smell) is among the first signs of AD and Parkinson’s Disease144,145.  
The behavioral symptoms that are a result of cognitive impairment and characterize AD are4:
·         Short term memory loss that disrupts daily life
·         Difficulty in planning and problem solving
·         Difficulty completing familiar tasks
·         Confusion with time and place
·         Confusion with visual and spatial relationships
·         Difficulty with word finding during speaking and writing
·         Increased daytime sleepiness*
·         Changes in mood and personality
·         Withdrawal from work or social activities
·        Decreased or poor judgement
*Sleepiness is measured by timing how long it takes for an individual to fall asleep while laying on a bed in a quite dark room.  The largest difference in sleepiness between non-AD (16min.), mild AD (11min.), and moderate AD (8min.) was observed at 10AM and 12PM146.  In those with dementia, including AD, sleepiness should not be confused with 5 to 20 second long fainting spells, called syncope, that start abruptly and end with spontaneous recovery147,148

Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that is a terminal illness with an average life expectancy of three to nine years post diagnosis.  The AD process occurs in stages 5 to 20 years before the first symptom of cognitive impairment is observed. The stages of AD are as follows: 
·         The first stage of this process involves aluminum facilitating the formation of small soluble protein fragments from amyloid precursor protein (APP), such as Aβ peptides and Aβ oligomers, and insoluble Aβ plaques between neurons. Aluminum conjugates of Aβ oligomers are much more neurotoxic than any other APP metabolite16. Aluminum’s epigenetic effect of lowering gene expression for both neprilysin and LDL Receptor LRP1, and increasing gene expression for both BACE1 and APP results in more Aβ peptides and Aβ oligomers, and insoluble Aβ plaques30,31 . Aluminum chloride with D-galactose has been found to create predementia in a mouse model for AD104The first stage of AD can be detected in humans as decreasing levels of Aβ peptides and Aβ oligomers in the cerebrospinal fluid.  These levels decrease as the peptides and oligomers are formed into insoluble Aβ plaques.  

·         The second stage of this process involves aluminum facilitating tau protein clumping together in tangles (NFTs).  Normally tau protein is used for microtubule assembly and stabilization in neurons. Aluminum’s epigenetic effect of lowering the production of the enzyme PP2A and aluminum’s inhibition of PP2A results in excess phosphoryl groups on tau22,99,100,136. Aluminum also facilitates the formation of NFTs from these over phosphorylated tau proteins24,25. NFT formation results in the death of neurons that are replaced with “tombstones” or “ghosts” of NFTs. The second stage can be detected as increasing levels of tau in cerebrospinal fluid.

·         The third stage is called mild cognitive impairment (MCI) and it occurs 1 to 4 years prior to a person being diagnosed with AD.  MCI is characterized by poor decision making and difficulty in remembering recent events and other lapses of memory.  These symptoms are due to aluminum causing microtubule loss, dendritic die-back, and cortical atrophy resulting in slow loss of memory149.  MCI can also be a symptom of metabolic (non-AD) dementia that may be curable (see Appendix II).

·         The fourth stage is called Alzheimer’s disease because it can be diagnosed as a slow loss of cognition with symptoms including difficulties with word recall and disorientation, such as getting lost, mood swings and behavioral issues.  These symptoms are due to substantial neuron damage and loss, called lesions, in areas of the brain related to short term and long term memory and decision making.  The severity of this stage can be gauged by performing either volumetric MRI to measure the shrinkages of the brain due to neurons expiring or FDG-PET that gauges the health of mitochondria in neurons.

If you are like me and have one or more aging parents, you may already have witnessed the slow decline of their short term memory. It is disturbing to realize they may have reached the 3rd stage of AD without even being aware their brains have the hallmarks of AD.  Also if you are like me you may worry that your own brain is beginning that downward spiral into AD.  Until recently it was only in the 4th stage that the disease could be diagnosed and called AD.  This late stage diagnosis of AD requires two major symptoms with short term memory loss usually being one of the two symptoms. 
According to the Alzheimer’s Association only 45% of those with AD or their caregivers report being told of an AD diagnosis. In part this is due to the difficulty in making the diagnosis. Until recently examination of brain tissue after death was required for a definitive diagnosis of AD.  The two hallmarks of AD histopathology are:
·         Neurofibrillary tangles (NFTs) inside neurons and “tombstones” or “ghosts” of former neurons in between living neurons.
·         Insoluble Aβ plaques formed from Aβ peptides and oligomers in between living neurons.
See sidebar on “Biochemistry and Neurochemistry of AD” for details on these two hallmarks.
One reason it has been difficult to prove what causes AD is that the symptoms of AD become apparent only in the 3rd and 4th stage and a definitive diagnosis of AD has required an autopsy.  A new class of ligands has recently been developed that allows for brain imaging by PET scans of both NFTs150 and Aβ plaques151. This allows researchers to follow the development of the hallmarks of AD histopathology in living patients.  These tests should facilitate our understanding of how aluminum and possibly other environmental toxins cause AD. These tests should also allow faster testing of drugs under development that will provide palliative relief from the symptoms of AD, if not a cure for AD. 
Conclusion of Alzheimer’s Disease
For the last 50 years, in spite of excellent research, the cause of Alzheimer’s has remained controversial.  It may be years before all the needed research is performed and the controversy ends. But now a tipping point has been reached and as described in this chapter there is convincing evidence that aluminum accumulation in our brains can cause Alzheimer’s disease.  Aluminum absorption in select areas of the human brain can result in the cognitive deterioration and associated cerebral pathology seen in AD as described in the following list:
·         Increased amyloid plaque formation in the brain that is a hallmark of AD
·         Increased phosphorylation of tau protein leading to neurofibrillary tangles (NFTs) that are a hallmark of AD
·         Inhibition of mitochondrial enzymes resulting in mitochondrial disease that is a clinical symptom of AD
·         Lesions in the perforant neuronal pathway resulting in loss of short term memory that is a behavioral symptom of AD
The presence of mixed cerebral pathologies becomes more common in individuals with advancing age. Forty-five percent of those over 90 with dementia had a multiple number of cerebral pathologies97. The presence of multiple pathologies is associated with increased likelihood and severity of dementia. AD as a single pathology is present in 28% of those over 90 without dementia and 23% with dementia. When a single additional pathology in addition to AD is present the chance of dementia is four times higher than with just AD pathology. When any three or more of these pathologies is present, the chance of dementia is 95% in those over 9097.  In addition to aluminum being a causal factor for AD, it has also been implicated as a casual factor for other cerebral pathologies (see Appendix I, III, and IV). For instance in Chapter 2 aluminum’s role as a causal factor for strokes and white matter disease is discussed. This is not to say that aluminum is the only cause of cerebral pathologies.  There are numerous environmental chemicals and several factors, such as head trauma, that have been implicated in cerebral pathologies (see Appendix I). Future research may find additional chemicals in our environment and additional factors that cause cerebral pathologies.
Since the commercial production of aluminum began, there has been a dramatic increase in AD cases worldwide.  There are cases of accidental and occupational exposure to aluminum that have shown that aluminum can cause both early-onset AD and the hallmarks of AD. 
The Alzheimer’s Association finds that Alzheimer’s disease is grossly misunderstood and underestimated.  When they surveyed people in 12 countries they found: 
 “59 percent of people surveyed incorrectly believe that Alzheimer's disease is a typical part of ageing”.

As a society we have made an incorrect assumption:
                “Because we now live longer, more of us will die of Alzheimer’s disease”   
This assumption is a self-fulfilling prophecy unless action is taken by individuals to lower their exposure to aluminum and society to improve regulations on the amount of aluminum in food, drink, and pharmaceuticals.  By lowering our aluminum ingestion and absorption we may be able to live longer without developing and suffering from AD. 
The people of Malaysia and Singapore have a much lower death rate due to AD than the U.S even though they have a similar life expectancy. Could the people of Malaysia and Singapore be ingesting a dissolved mineral called OSA that increases aluminum excretion by their bodies?  See Chapter 5 for the answers to these questions. In Chapter 4 we will discuss ways to avoid or lower aluminum ingestion and in Chapter 5 we will discuss how to decrease aluminum absorption by your brain after ingesting aluminum.  

Chapter 1 Part 8 The Case for Aluminum Being the Cause of AD - continued

8)      Analogy of metal neurotoxicity to diseases similar to AD:
The two best analogies for a trace metal in the environment causing a disease, such as aluminum causing AD, are the effects of lead or mercury accumulation in our brains. Like aluminum both of these metals slowly accumulate in our bodies over our lifetime and cause mental illness.
Low level lead exposure was common during the Roman Empire.  The people of this period used lead to make water pipes, cookware, and cosmetics.  Corrosion of lead in contact with their drinking water and application of leaded cosmetics to their skin resulted in lead accumulation in their bones and brains141.  Judging from the amount of lead found in their bones, these people suffered from mild to severe lead poisoning resulting in brain swelling that caused severe headaches, confusion, irritability, seizures, and possibly death. Lead exposure continues today as there is lead in drinking water due to lead water pipes and lead pollution in ground water. For more information on the analogy between lead and aluminum exposure see Chapter 8.
Low level mercury exposure is currently common.  Mercury gets into the environment from both human-generated sources, such as coal-burning power plants, and natural sources, such as volcanoes. Consumption of fish is the primary ingestion-related source of mercury in humans.  The mercury in both salt and fresh water organisms is bio-concentrated in the food-chain that ends up in fish and humans. Symptoms of mercury poisoning typically include lack of coordination and sensory impairment, such as vision, hearing, speech, and sensation.  Although these symptoms indicate brain damage, mercury also damages the kidneys and lungs and can lead to death.   
9)      Experimental evidence showing that AD can be prevented:   
The primary goal of this book is to show that diseases caused by aluminum can be prevented by 7 supplements, 7 lifestyle choices, and a dissolved mineral.  For example AD may be prevented by, antioxidants that counteract the oxidative effects of aluminum (Chapter 3), avoidance or minimization of aluminum exposure (Chapter 4), a complexation agent and vitamin that lower brain aluminum accumulation (Chapter 3 and 5), and a combination of aerobic exercise and sleep (Chapter 6).      
·         The antioxidant PQQ protects the brain from low level aluminum exposure by inhibiting the formation of reactive oxygen species (ROS) and reducing ROS as they form in the brain due to aluminum accumulation.
·         Avoiding foods and pharmaceuticals, like antacids, that are high in aluminum, filtering drinking water, and cooking in non-aluminum cookware minimizes aluminum exposure.
·         Orthosilicic acid taken orally is absorbed into the blood and complexes with aluminum facilitating its excretion by the kidneys.
·         Vitamin D3 taken orally is converted by the body to vitamin D that facilitates the excretion of aluminum by the kidneys, even in the case of damaged kidneys due to kidney disease. 
·         Aerobic exercise and sleep help to cleanse the brain of Aβ peptides and oligomers that are complexed with aluminum.
 The best evidence that AD can be prevented is comparing the AD rate in countries with high levels orthosilicic acid in their drinking water, such as Singapore and Malaysia, with countries with low levels of orthosilicic acid in their drinking water, such as the U.S. and Iceland.  

With comparable life expectancy and higher orthosilicic acid in their drinking water, people who live in Malaysia and Singapore have a much lower death rate due to AD.  Since orthosilicic acid facilitates the excretion of aluminum by the kidneys, there is evidence that lowering aluminum will prevent AD.
 Conclusion: The nine criteria of causality originally set out by Sir Austin Bradford Hill72 and applied to neuropsychiatric conditions, such as AD, by Robert Van Reekum73 have been applied using primarily human data taken from studying AD patients and controls. The conclusions are that aluminum is the likely cause of AD and AD is a human form of chronic aluminum neurotoxicity.  Given these conclusions we as individuals and a society have a responsibility to take action.  This book proposes what action can and needs to be taken to avoid or lower our exposure to aluminum and prevent diseases caused by aluminum.      

Aluminum an Unrequired and Unwanted Intruder

People representing the aluminum industry routinely point to aluminum’s omnipresence in our bodies as a sign of its essentiality. It is true that we all currently have a body-burden of aluminum but there has been no proven benefit of aluminum in our bodies.  In fact aluminum is a neurotoxin and aluminum exposure is the known cause of a number human diseases142

The brain relies on a delicate balance of monovalent (e.g. potassium and sodium) and divalent (e.g. calcium, magnesium, and zinc) cations in order to function properly.  These cations bind reversibly and not tightly with aminoacids, such as histidine and lysine that are involved in the active sites of key enzymes (e.g. protein phosphatase) or on the backbones of key proteins (e.g. β-amyloid and α-synuclein).  Aluminum is a small trivalent cation that can bind tightly to both key enzymes and proteins in the brain.  For instance magnesium regulates over 300 proteins and aluminum competes for magnesium binding. Aluminum binds to some of these proteins 10 million times stronger and dissociates 10 thousand times slower than magnesium143. This property results in aluminum’s slow accumulation in select areas of the brain and aluminum’s inhibition of enzymes that causes the onset and progression of AD and possibly other forms of dementia. Aluminum is an unrequired neurotoxic element and not a nutrient for normal body function.  This makes aluminum an unwanted intruder. 

Chapter 1 Part 7 The Case for Aluminum Being the Cause of AD - continued

4)      Temporality of aluminum accumulation occurring before AD: 
This criterion requires that the causative agent occurs prior to the outcome.  Therefore chronic aluminum exposure must precede AD if chronic aluminum intake is the environmental cause of AD.
For the last 125 years we have lived in the “aluminum age” during which there has been a steady increase in our exposure to aluminum. We ingest food, pharmaceuticals, and drink water containing aluminum, we apply aluminum containing products to our skin, we are vaccinated with aluminum containing vaccines, and we inhale air containing aluminum112.  This results in a slow accumulation of aluminum in our brains from the fetal stage to old age28,49,113,114.      Therefore humans living in an industrialized society accumulate aluminum in certain regions of their brains many years before the onset of AD.  There are three sub-cellular changes in brain physiology that occur prior to overt AD in humans and all three lead to AD:
·         Progressive aluminum accumulation in neurons
·         Hyperphosphorylation of tau due to aluminum inhibition of an enzyme
·         Oxidative stress due to aluminum
Increasing aluminum exposure and accumulation is in lock-step with the increasing frequency of AD.  AD was described as a rare disease in The Lancet fifteen years after Alzheimer’s 1911 paper115. The reported number of AD cases rose from one in 1907 to more than 90 by 1935116.  Subsequently the age-adjusted death rate for AD in the U.S. rose from 0.4 per 100,000 in 1979 to 25 per 100,000 in 2010117,118. In the 25 year span from 1980 to 2004 the annual U.S. death rate from AD in those over 65 rose from 1,037 to 65,313 per year117.     
It is estimated that in North America the mean aluminum intake is 24mg of aluminum per day, equivalent to more than 8.76 grams per year118.   The demand for aluminum products has increased requiring more and more aluminum be extracted and refined from bauxite deposits.  The current annual global demand for aluminum is 11 kg per person119.  This means approximately 0.08% of the aluminum produced each year is ingested.  Demand for aluminum has increased 30-fold since 1950 and is estimated to increase by 3-fold current levels by 2050119.  Using these data on aluminum demand, it is estimated that human exposure to aluminum has and will continue to increase at a rate of 90 fold over the 100 year period from 1950 to 205039.  This means we only ingested 0.29 grams of aluminum per year in 1950 and by 2050 we will be ingesting more than 26 grams per year. 
So temporality exists as aluminum accumulates in our bodies prior to the onset of AD.  In addition the rate of ingestion and accumulation of aluminum is increasing and this accounts for the rising prevalence of AD.
5)      Biological Gradient with Dose-response Effects of Aluminum and AD: 
In 1996 McLachlan, et al. observed a dose-response in the amount of aluminum in drinking water with the risk of AD in humans75.  Each subject’s residential and drinking water history for the 10-year period prior to death were taken into account.  The drinking water subjects were exposed to varied from less than 100mcg/L to 175mcg/L.  A single pathologist performed a histopathological examination of all 614 brains included in this study. The brains were assigned to AD or control groups based upon clinical history and the presence or absence of plaques and NFTs. The results in the following table demonstrate a dose-response relationship between aluminum in drinking water and AD.

6)      Biological Plausibility of Aluminum Neurotoxicity Causing AD:
It is known that aluminum facilitates the formation of Aβ plaques and NFTs in the brain that are two hallmarks of AD16,17,24,25. Aluminum causes oxidative stress that kills mitochondria and ultimately kills neurons53.  This results in mitochondrial disease and increased atrophy of some brain regions both of which are clinical symptoms of AD. Aluminum also disrupts memory storage that is a behavioral symptom of AD44
Some metal ions, such as aluminum, act as physiological stressors in the brain by stimulating brain cells to produce oxidizing chemicals (a.k.a. ROS)121,122. This ROS can damage and kill mitochondria and neurons creating inflammation in the brain. Aluminum tops the list of metal ion inducers of ROS in human brain’s glial cells58.
It has been observed from microscopic evidence that aluminum causes lesions in the brain’s perforant pathway that result in short term memory loss44.  Aluminum also acts as individual ions to block the neurochemistry of long and short term memory storage123. This mechanism of action explains why very small amounts of aluminum in the brain (i.e. on the order of several parts per million or micrograms per gram of brain on a dry weight basis) can have a very large impact on memory storage.
Calmodulin is a calcium-binding messenger protein required for memory formation and storage.  Aluminum ions modify its structure thereby inhibiting its function123.  This prevents calmodulin from regulating calcium levels in neurons and also prevents the activation of four key enzymes that control memory formation and storage in neurons.
The neurochemical explanation of how memories are stored in neural networks is still evolving. However considerable detail has already been discovered.  The ground-work was laid by Donald Hebb in 1949124 when he described a theory of neuronal learning as:
“Neurons that fire together - wire together and neurons that are out of sync - do not link”.
The neurochemical mechanism that supports Hebbian Theory involves the synchronized firing of several different types of neuroreceptors at a synapse between two neurons.  When this occurs in synchrony it leads first to stronger or potentiated neuronal connection between the two neurons.  This connection is then made even stronger by several types of neuroreceptors moving their location in order to increase their density at the synapse.  The theory that describes this two- step process of strengthening neuro-circuits is called spike-timing dependent plasticity (STDP)125.  The successful result of this process is called long term potentiation (LTP).  STDP and LTP are theorized to be the way memories are stored.  A lack of synchrony in the process leads to no potentiation and is called long term depression (LTD) or lost memories.  Aluminum ions inhibit calmodulin from activating four key enzymes involved in LTP16,101,123,126-129. Thereby aluminum ions encourage LTD and cause memory loss (see Neurochemistry of Memory Impairment by Aluminum for details on role of these four enzymes in memory storage).
The biological plausibility of aluminum causing AD is well established by those studies that have connected aluminum’s neurotoxicity with the hallmarks and symptoms of AD.
7)      Coherence of what we know about how aluminum neurotoxicity causes AD:
Aluminum taken in by ingestion alone is estimated to be 24mg a day of which approximately 0.2% is absorbed into our blood118,130,131We know that aluminum accumulates more in some areas of the human brain such as memory processing regions86.  This accumulation likely results in chronic aluminum neurotoxicity and the hallmarks and symptoms of AD.  The cells in these regions have very high energy needs.  The high rate of energy utilization increases the demand for iron.  Transferrin is the molecule that carries iron to these cells.  Therefore these cells have a high density of transferrin receptors on their membrane in order to facilitate iron uptake.  Aluminum and iron ions are almost equivalent in size and can have the same ionic charge.  This allows aluminum to be carried by transferrin into these cells in higher than normal amounts even though the cells have no need for aluminum. 
Some metal ions act as physiological stressors in the brain by stimulating brain cells to produce oxidizing chemicals (a.k.a. ROS)121,122. The metal ions stimulate inducible nitric oxide synthase (iNOS) in microglial and astroglial cells of the brain to produce nitric oxide (NO) that reacts to produce ROS122. This ROS can damage and kill neurons creating inflammation in the brain.  The following table shows how much ROS is produced from a cell culture of human glial cells exposed to 50nM aqueous solutions of various common metal ions58.  Aluminum tops the list of metal ion inducers of ROS in human brain’s glial cells.

The brain damage caused by aluminum inducing ROS could partially account for the neuronal death that underlies brain atrophy. This atrophy is seen in those areas the brain that are aluminum “hot spots” and it parallels aluminum accumulation in those areas of our brains as we age86,94.
Neurofibrillary tangle (NFT) formation in the brain is a hallmark of AD.  Aluminum has been shown to participate in NFT formation in both pre-tangle and tangle-bearing cells132.   Aluminum inhibits the activity of enzyme PP2A that clips off excess phosphoryl groups on a structural protein of the brain called tau22,133. Aluminum also inhibits the expression of a gene involved in making PP2A100. Aluminum creates a lack of active PP2A that results in tau being coated with more than the normal number of phosphoryl groups. This accounts for low PP2A activity and paired helical filaments (PHFt) found in the brains of AD patients133. In AD brains aluminum secondarily aggregates the PHFt into granules that fuse and grow into cytoplasmic pools of PHFt and aluminum that give rise to NFT filaments132. Aluminum and PHFt give rise to NFTs in brain cells, including large pyramidal and stellate cells, particularly in the brains of those with AD132.   Pyramidal cells are found in many regions of the brain, including the hippocampus, entorhinal, and prefrontal cortex.
Aβ plaque formation in the brain is another hallmark of AD.  Aβ plaques form from Aβ peptides that are cleaved from large Aβ precursor proteins (APP).  This process is called amyloidogenic cleavage and alteration of this process is a key feature of AD134.  Beneficial non-amyloidogenic cleavage of APP leads to a secreted product that is important for promoting neurite growth and maintaining brain tissue.  Protein phosphorylation stimulates the beneficial non-amyloidogenic pathway.  Both protein kinase C (PKC) activity that increases phosphorylation and protein phosphatase 2A (PP2A) activity that decreases phosphorylation are involved in the control of how much of each competing pathway is used for APP cleavage135. Activation of PKC decreases production of Aβ peptides by 50-80% and increases the beneficial non-amyloidogenic cleavage by 30-50%135. Nanomolar concentrations of aluminum reduce PKC activity by 90%136.  Therefore inhibition of PKC activity by aluminum directs APP to the amyloidogenic pathway resulting in more Aβ peptide135.   This situation is partially modulated by aluminum’s inhibition of PP2A135.
Microtubules are important neuronal structural features that are required for strength, rigidity, and transportation of cell constituents between the nucleus of the cell and the synapses.  Human pyramidal cells that contain NFTs and/or high levels of aluminum accumulation are microtubule-depleted44.  Aluminum-induced microtubule depletion is possibly more fundamental to AD neuropathology than AB oligomers, AB plaques, or NFTs74. This is because microtubule depletion is more damaging to neuronal connectivity and function than these hallmarks of AD neuropathology that may represent protective cell responses to aluminum 132,137. Aluminum-induced microtubule depleted cells have axonal and dendritic dieback that is consistent with AD being associated with neuronal disconnection.   In addition aluminum-induced microtubule depletion leads to synapse breakdown and depletion44,138. This explains why humans with AD have impaired axonal transport139,140.

Neuronal death is marked in the brain by ghost NFTs that can be the result of aluminum accumulation in the neuron prior to death.  NFTs inside the pyramidal cells tend to displace the cell nucleus to the periphery resulting in denucleation. The denucleated cell is unable to renew cellular membranes and eventually the cell membrane ruptures74.  This results in an extracellular ghost NFTs that act as tombstones of former neurons and a hallmark of AD.