Q&A on wide-ranging topics, currently including genetic
basis, symptoms and prevalence of Alzheimer's disease,
genetic basis of multi-infarct dementia, schizophrenia
and Alzheimer's disease. Please feel free to contribute
comments and questions.
Topic: Down Syndrome
Question from TH Vandoren:
Has there been any research or ideas regarding use of Aricept in a Down
syndrome patient who has not yet shown changes similiar to dementia?
Response from Dr. Ken Kosik, Harvard Medical School:
"Because Aricept has no effect on the underlying pathogenetic mechanism
of the disease; rather it falls in the category of a neurotransmitter
replacement--I would not see an indication in presymptomatic disease
whether due to trisomy 21 or any other cause."
Response from Dr. Peter Davies, Albert Einstein College of Medicine:
The idea of treating Down's patients is controversial. What does
informed consent mean in this population? Likewise, the diagnosis of
Alzheimer's Disease in this population is very difficult, given that the
mean IQ is about 45. I would not expect Aricept or Cognex to do anything
in Down's prior to the onset of the Alzheimer's Disease and degeneration of
the cholinergic neurons. Neither of these drugs is expected to postpone
or slow the process of degeneration: they simply may compensate somewhat
for the lack of acetyl choline caused by the degeneration of cholinergic
neurons. In a population of Down's aged over 40 (and thus presumed to
have Alzheimer pathology, including the cholinergic deficiency), one might
predict small improvements in cognitive function, to about the same
extent that one sees in non-Down's Alzheimer patients. But then again, the
issues about cognitive tests that might be appropriate to measure this
"improvement" again would be difficult in these patients. One would need
a carefully designed study, with special behavioral testing appropriate
for the Down's population, to determine if these drugs did anything. Then
perhaps some discussion of the ethical issues may need to be raised.
Question from Ness Bashara:
Topic: Aluminum and Alzheimer's Disease
Comment by Paolo F.Zatta (Zatta@cribi1.bio.unipd.it)
Recent literature has presented new data regarding the controversial
Aluminum hypothesis on A.D.However, since the majority of scientists
are either not experts in aluminum chemistry or involved in other
aspects of the problem these data have been disregarded. It could
be interesting to have the possibility to discuss if the aluminum
hypothesis is still alive as I and other belive. In this connection
we have open a Web page open to everyboby interested in the study
of aluminum toxicology. The number is
Someone just told me that one gets 3.9% of alumin. from pop cans.
This concerns me. Can you validate or tell me what the reasearch
currently has learned? I ask, because I have been a HEAVY alumin. pop
can user for 10 years, AND I am experiencing memory loss. It's minor to
moderate so far. I am only 47 years old, so I am also intrested in what,
if anything can be done to test for alum in the brain, and what
I do appreciate any help you can provide.
Response by Dr. Peter Davies, Albert Einstein College of Medicine
From my point of view, the aluminum issue in Alzheimer's Disease is essentially dead.
Despite decades of work, it is clear that aluminum given to animals (or accidentally to humans)
does not cause Alzheimer's Disease. This is not to say that one cannot demonstrate neurotoxicity
of aluminum if it is given in the right salt form into the brains of some animals. However, even
in these rather extraordinary circumstances, the pathology that results is NOT that of
Alzheimer's Disease. Humans exposed to huge amounts of intravenous aluminum (through dialysis
back in the 60's, in some countries) may suffer neurotoxicity, but again, do not appear to
develop the pathology of Alzheimer's Disease with any reasonable frequency. Thus experimental
work in this area, while not entirely over, is now at a very low level.
Response by David W. Walker (email@example.com) -- Posted 28 August 2001
All aluminum beverage containers are coated with an inert polymer to keep the liquid and metal can separated. This is done primarily to protect the taste of the product. If this coating is damaged or missing and a significant amount of aluminum has leached into the product, the beverage will almost certainly have a noticable off-taste that would keep most people from finishing the can. Therefore, it would be highly unlikely that anyone would consume a canned soft drink or juice with a high aluminum level and not be aware of it. The typical amount of aluminum in canned beverages with an intact polymer barrier is the same as, or lower than, the public water supply used to manufacture them - that is to say, it is extremely low. Beverages in aluminum cans do not have anything close to the 4% aluminum mentioned by Bashara, but this continues to be a common mis-preception and a persistant internet rumor.
Topic: Genetic basis of Alzheimer's disease, symptoms,
Q: What happens to the chromosomes?
Which chromosomes are affected in AD?
What are the odds and frequency of getting this disease?
What are the symptons? When do you die?
--Ian Michael Smillie
A: There are four genes that have now been linked to Alzheimer's
disease. Three are implicated in inherited forms of AD, with onset at
around age 30-50. These are the genes for amyloid precursor protein
(APP), on chromosome 21, and two highly homologous proteins known as
presenilin 1 and 2, located on chromosomes 1 and 14. The fourth gene,
for apolipoprotein E (ApoE), is located on chromosome 19 and its E4
allele is considered to be a risk factor for late onset AD. In the three
genes for early onset AD, the fault appears to lie in a variety of
mutations that affect the functioning of the gene products in ways that
are still being elucidated. All of these mutations appear to increase
the production of a specific, 42-amino-acid form of beta amyloid
peptide, which is theorized to cause neuronal degeneration and death in
Alzheimer's disease. For further information on the amyloid theory, see
on-line seminar by Dennis Selkoe.
With the ApoE gene, there appears to be an increased risk
associated with one of the common alleles. A disproportionate number of
AD patients have at least one E4 allele. However, the allele only
contributes to risk. There are many people with one or two E4 alleles
who live to an old age without any sign of dementia. See the Alzheimer
Molecular Genetics page for further details.
A few researchers such as
Peter Davies at Albert Einstein College of Medicine in New York and
Huntington Potter at Harvard Medical School are also interested in the
theory that AD may be linked to an increased propensity for chromosome
21 disjunction. People with Down's syndrome, caused by having an extra
copy of chromosome 21 ("trisomy 21"), almost inevitably develop AD at a
young age. Down's syndrome is caused by chromosome disjunction during
the formation of ova. A study of women who gave birth to Down's babies
before age 35 found that these women later developed AD at a
disporportionately high rate. This gave rise to speculation that there
is some kind of inherited disorder involving chromosome 21 disjunction.
If the disorder affects the germ line, then Down's syndrome is the
result. But if it affects cells in the brain during development, it
might result in a smattering of trisomy 21 neurons that contribute to
late onset AD. This is so far a theory, with some intriguing evidence to
support it, but by no means proven yet.
Currently about 4 million Americans are affected. AD is the most
common cause of dementia among people age 65 and older. (But many senile
dementias have other causes, including stroke, depression, reactions to
medications, etc., which can be treated.) It is thought that nearly half
of all people age 85 and older have AD.
The symptoms involve a progressive, irreversible decline in
memory and thinking abilities. The decline is related to a loss of
neuron function, connections and eventually of the neurons themselves.
On average, AD lasts from 4 to 8 years after diagnosis. However, it can
continue for up to 20 years.
--June Kinoshita, Alzheimer Research Forum
Topic: Multi-infarct dementia
Q: Excellent site. Would like to see more info on Multiple infarct
dementia. Alzheimer information is much more developed than for other
forms of dementia. My grandfather died when my father was 2 years
old, but my father (68 yrs ofd) and virtually all of his 3 aged brothers
have been afflicted with dementia in the form of multi-infarct. I have
found nothing on genetic disposition of this vascular disease nor
medical practitioners who know much more than treatment of the
symptoms.Thanks for your good work.
--Michael Couch, 11/14/96
A: This is a long and complex subject. There are several authorities
interested in MID. I would consult Dr. Vladimir Hachinski , London,
Ontario (Ph: 519 663-3652; Fax 519 663-3982) or Dr. Dennis Dickson at
the Department of Pathology, Albert Einstein College of Medicine, Bronx. NY.
-- Dennis Selkoe, 1/3/97
A: Now that you have put multi-infarct dementia on my radar screen, I
can refer you to a recent paper on the subject that might be of interest
to you. A group in France recently reported that the gene for Notch-3 is
the site for the mutation that causes a disease called CADASIL, an
autosomal dominant, inherited form of multi-infarct subcortical
dementia. The paper was published by Elizabeth Tournier-Lasseve, et al.,
in Nature, Vol. 383, p. 707-710.
-- June Kinoshita, Alzheimer Research Forum
Topic: Schizophrenia and Alzheimer's
First of all I would like to congratulate you and thank you all for the
outstanding service you provide. I would very much appreciate if you
would be so kind in providing me with information about Schizophrenia
and Alzheimer's disease. I am currently involved in a reserch project
which involves the normal neuroanatomy and neurophysiology of
neurotransmitters, as well as the pathophysiology of Schizophrenia and
Alzheimer's disease, with emphasis on the alterations in
neurotransmisson and the anatomoclinical correlations that explain their
clinical feaures. I apologize for the extend of this message and thank
you for the time you may take to consider my request. This is a very
important project and your help is very much appreciated.