Chapter 1 – Alzheimer’s Disease
“… anatomically it provided a result which
departed from all previously known disease pathology.” L. Alzheimer 19071
What Causes Alzheimer’s Disease?
The book begins as I did,
searching for the cause of Alzheimer’s. I initiated this search when
simultaneously my mother and a friend’s mother began having panic attacks due
to short term memory failure at age 85. The progression of short term memory
loss had been slow and steady and was just beginning to impact their daily
living skills. Routine things they had
done on a daily basis, such as grocery shopping, balancing the checkbook, and sewing,
had become impossible tasks. I hoped that learning what was known about the
cause of Alzheimer’s would allow me to help these women slow the progression of
the disease and possibly prevent further erosion of their memories.
I quickly discovered that finding the cause versus symptom of a disease like
Alzheimer’s is a tricky business. It
takes a sleuth with the knowledge and cunning of Sherlock Holmes. Being a chemist I have always had a
fascination with Mr. Holmes, probably because he was portrayed as a chemist by
Sir Arthur Conan Doyle. Young Stamford said Holmes was a “first-class chemist”
when he first introduced Watson to Holmes in “A Study in Scarlet”. In order to understand my search for a cause
of Alzheimer’s (AD) please follow Mr. Holmes and Doctor Watson and read “The
Case of the Cloaked Assassin”.
The Case of the Cloaked Assassin
Watson we may have a killer
loose on the streets! I just read on the
internet in the Journal of Medical Case Reports 8:41 (2014) of the strange death
of a 58 year old man with no prior medical history who was diagnosed with early-onset
AD. Ten years prior to his diagnosis he
began working on a daily basis handling alum dust in order to develop a new
insulation for the nuclear and space industry. He was working with minimal respiratory
protection. After six years performing
this work he began suffering from memory loss and depression. In 2011, after his death due to AD at age 66,
the frontal lobe of his brain was analyzed for aluminum. It contained approximately 3mcg (3 micrograms)
of aluminum per gram of dried brain tissue (3mcg/gr. dry wt.)2. This is more than three times higher than the
median concentration of aluminum (e.g. 0.87mcg/gr. dry wt.) found after death
in the frontal lobes of people 60-70 years old3. In addition, an abundance of beta-amyloid (Aβ) plaque and a profusion of neurofibrillary tangles (NFTs), hallmarks of
AD, were found in his frontal cortex.
So Watson what is coincidence
and what caused AD in this case of strange death? There are four
possibilities:
·
The victim was genetically
predisposed toward AD
·
Aβ plaques were the cause of
AD
·
NFTs were the cause of AD
·
Alum was the cause of AD
The first question – what are Aβ plaques and NFTs? These plaques and NFTs are insoluble protein molecules that are
three dimensional aggregates of smaller soluble molecules called peptides and
oligomers that are comprised of amino acids.
An amino acid is a molecule with at least one each of an amine and acid.
Amyloid beta (Aβ) plaques are
made from Aβ oligomers that are aggregates of Aβ peptides that are in turn fragments
enzymatically cleaved from a larger protein called amyloid precursor protein
(APP).
NFTs are filaments of a phosphoprotein
called tau that stabilizes structural elements in neurons called microtubules.
Tau has 79 potential sites for phosphorylation. Thirty of these sites are
usually phosphorylated in normal tau proteins giving them an overcoat of
phosphorus, oxygen and hydrogen. The tau in NFTs is more highly phosphorylated
than normal and is called hyper-phosphorylated tau.
The second question - what is in alum? Alum is a combination of
aluminum and sulfate ions making a salt. In some cases alum salts also include
other ions such as in ammonium alum (a.k.a. ammonium aluminum sulphate), and potassium alum
(a.k.a. potassium aluminum sulphate, potash alum).
After
hearing this definition of alum as being a salt of aluminium sulphate, Doctor Watson
became agitated and said: “Wait just a minute Holmes, as a medical doctor I
believe aluminium should not be on the list of suspects for AD!” Watson pointed
out that according to the Alzheimer’s Association “… studies have failed to confirm any role for aluminum in causing
Alzheimer’s”4. Holmes turned to Watson and replied: I applaud you,
your profession, and the Alzheimer’s Association for their dedication to caring
for and supporting those with illnesses and their mission to eliminate
Alzheimer’s disease through the advancement of research and the promotion of
brain health. But historically there have been examples when the medical
profession has not been sufficiently open-minded to explore all the potential causes
of a disease.
One
such example of a missed opportunity to save lives was the prevention of pellagra.
Pellagra results in dementia, painful disfigurement, and death and is now known
to be caused by a lack of niacin in the diet.
Niacin is concentrated
in the outer-most layer of the endosperm and germ layers of the corn kernel
that are removed by milling. In 1901 the Beall
Degerminator was patented that could mill the corn removing the outer endosperm
and germ layers from the kernels for improved storage. In the southern part of
the U.S. between 1906 and 1940 mechanical corn milling resulted in 3 million
people sickened by pellagra and more than 100,000 deaths due to pellagra. In
1913 Casmir Funk wrote an article suggested that the new procedure for corn milling
was causing pellagra, but he was ignored5. The medical profession in
the U.S. firmly believed a toxin in rancid unripe corn was the cause of
pellagra6. It took a number of years after the connection between
niacin deficiency and pellagra was discovered for the medical profession to
finally abandon their toxin theory. So as you can see Watson we should remain open-minded and leave
aluminium on the list of suspects for AD so we do not repeat any missed
opportunities to save lives.
Watson,
who was still pondering this dilemma regarding aluminium as a suspect,
responded: “I am all for saving lives and I know that aluminum is a proven to
be toxic to neurons but I have read and believe the following:”
·
Aluminum compounds are inert or insoluble preventing
entry into the body.
·
Any aluminum that does get into the body is
immediately excreted.
·
Any aluminum that is not excreted is deposited in
biologically inert stores such as bone.
Dear Watson
we may find comfort in believing this dogma but these are untrue myths that give
us a false sense of security. Aluminum
can cloak itself in a variety of chemical disguises and enter the body through
the gut, skin, lung, and nose.
Acidification of aluminum compounds in the environment by acid rain and
in the gut by stomach acid, solubilizes these compounds and allows aluminum the
freedom to change its chemical disguise. Once in the body some of the disguised
aluminum finds its way to the brain and accumulates in our brain during our
lifetime. I know these facts are
unpleasant to deal with, but facing reality is better than keeping our heads in
the sand. So Watson let’s proceed ahead
with aluminum on the suspect list and see where this investigation takes us.
The third
question that begs an answer is how old is Alzheimer’s disease? Is AD an ancient disease that happened to
finally get a diagnosis or is it a modern disease? At age 35 in 1901 Doctor Alois Alzheimer began
observing a patient named Auguste Deter in a Frankfort Germany asylum. She had strange behavioral symptoms and had
lost her short term memory. After she
died in 1906 her brain was autopsied by Dr. Alzheimer. Using special stains he
found amyloid plaques and neurofibrillary tangles. So let’s ask the doctor himself if AD is a
modern disease. After an exchange of
letters, Holmes had the answer. In a translation of Dr. Alzheimer’s words:
“The case presented
even in the clinic such a different picture, that it could not be categorized
under known disease headings, and also anatomically it provided a result which
departed from all previously known disease pathology”1.
Doctor Alzheimer
believed AD is a modern disease but did anyone else share his opinion?
The mental health of older people living between 1886 and 1889 is
described in the monograph “Old Age” published in Cambridge England in 18897. The monograph summarizes the results of
British general practitioners studying the mental health of their oldest
patients during the mid-1880s. The study
group was 900 subjects who were 80 or older including 74 centenarians. The monograph’s author concludes that
dementia:
“… was
witnessed only in two of our centenarians … indeed the brain held out as well
or better than other organs”
This 3% rate of dementia among
centenarians in the mid-1880s can be compared with a study 111 years
later. In 2000 a study was done of
people in three Dutch towns with populations greater than 250,000. Of the 17 centenarians found in this more
recent study 15 had dementia for an 88% rate of dementia. The other 2 centenarians could not be
examined8.
From Doctor Alzheimer’s
comments in 1907 and comparing these two studies of dementia among centenarians
done 111 years apart, it is obvious Watson that AD is a modern disease that is between
110 and 180 years old. So now Watson let us look at the first suspect:
genetics.
