Their genetically altered mice regained the ability to navigate mazes
after the genes that caused their dementia were de-activated.

This suggests that the brain damage caused by Alzheimer's is not
permanent, they wrote in their report, published in the journal Science.

``I was astonished. I didn't believe the results when I saw them,'' said
Alzheimer's researcher Karen Ashe of the University of Minnesota, who
led the study.

``When I saw the memory getting better I actually thought I had done
something wrong in the experiment.''

Alzheimer's is a brain-destroying disease that affects an estimated 4.5
million people in the United States alone and millions more globally. As
the population gets steadily older, experts estimate this number will
balloon to as many as 16 million by 2015 in the United States.
Outward symptoms start with memory loss, which progresses to complete
helplessness as brain cells are destroyed. In the brain, neurons die as
messy plaques and tangles of protein form.

The two proteins involved are unhealthy forms of natural brain compounds
called amyloid beta and tau protein.

Ashe's team worked with mice genetically engineered to develop the
mutant tau, but this mutation could be stopped -- or de-activated --
*_with use of a drug called doxycycline.
_*As expected, the mice developed dementia and had brain atrophy similar
to human Alzheimer's disease.

And when the engineered gene was turned off, memory loss stopped, as
expected. But the mice did not merely stop getting worse. They got better.

``Even mice that had lost half the neurons that are involved in forming
memories, when we removed the molecule causing the memory loss from the
remaining neurons by turning off the genes, the mice were able to learn
and remember new information,'' Ashe said in a telephone interview.

``No one suspected so many neurons would still be able to function.''

From mice to men
She noted that it is a long way from treating a mouse to treating a person.
``How are we ever going to turn off the gene in humans?'' Ashe asked. What
might be possible, she said, would be stopping the production of the
mutant proteins. And current vaccine efforts are aimed at removing the
bad proteins from the brain.

``The point that makes us hopeful is the remaining neurons were
functioning,'' she said. ``When we removed the molecules that presumably
were causing the malfunction, the mice were able to perform better.''

Ashe said her team used a swimming maze test, in which mice must swim
and find an underwater platform to stand on.

``The maze situation is very similar to parking a car in the parking lot
and remembering where you parked it,'' she said.

William Thies, vice president for medical affairs at the Alzheimer's
Association, said at the very least the mouse would be a useful tool for
testing new therapies.

``It at least opens the possibility that people will get better,'' Thies
said in a telephone interview.
The other interesting finding, Ashe said, was that the tangles of brain
cells were not in themselves, evidently, toxic to surrounding brain tissue.

``The neurofibrillary tangles, which are one of two major pathological
hallmarks of Alzheimer's disease, turn out not to be involved in causing
memory problems, at least in mice,'' she said.
Some process may be going on at a microscopic level, and the tangles may
be a result but not a cause of the brain damage, she said.

Copyright 2005 Reuters Limited

The hallmark of Alzheimer's disease is plaque formation in areas of the brain that control memory and thinking skills.

While the cause of Alzheimer's disease remains unknown, the researchers say that evidence indicates that plaque formation and accumulation may play a role.

In a recent experiment, scientists succeeded in deleting plaque in mice with a disease similar to Alzheimer's. The mice's brain cells also bounced back, to some extent, from plaque damage.

The experiment was conducted by researchers including Robert Brendza, PhD, a research instructor in the neurology department at Washington University School of Medicine in St. Louis. Their findings appear in the online edition of The Journal of Clinical Investigation.

Targeting Plaque

The researchers used ANTIBODIES to clear away the plaque. The antibodies targeted a PROTEIN called Abeta (amyloid beta), which is a key ingredient of the plaque seen in Alzheimer's disease.

The antibodies were injected directly onto the mice's brains. Afterwards, the researchers watched to see what happened next.

To peek inside the heads of the mice, the researchers put the living animals under the microscope. With a little help from fluorescent dye, the scientists could see how the brains of the mice fared.

The scientists didn't have to wait long. The antibodies went to work quickly. After three days, plaque was sharply reduced. A "rapid reversal" was also seen in plaque-related brain injuries, say the researchers.

SOURCES: Brendza, R. The Journal of Clinical Investigation, online edition. News release, Washington University School of Medicine.

Alzheimer's disease has been associated with a deficit of the neurotransmitter, acetylcholine, in the brain (10). One possible cause is a decrease in the enzyme that converts choline into acetylcholine in the brain.
http://lpi.oregonstate.edu/infocenter/othernuts/choline/

This hypothesis has been supported by repeated findings that pathological mechanisms associated with Alzheimer's disease invariably end up being related to learning mechanisms (e.g., acetylcholine, norepinephrine, serotonin pathways, NMDA receptors, synapse counts, tau phosphorylation, Amyloid PreProtein, cerebral cholesterol metabolism; see Ashford, Mattson, Kumar, 1998).

The neuroplasticity hypothesis also pulls together the tau and amyloid hypotheses with the corollary hypothesis that there are two fundamental cellular memory mechanisms, each attacked by one of two types of pathology, the first by the amyloid (more closely linked to causation, affecting more diffuse cortical regions including the temporal and parietal lobes), resulting in senile plaques, then, once a critical point is reached, the second by tau hyperphosphorylation, which leads to the neurofibrillary pathology (correlated with dementia severity, initially affecting the hippocampus and medial temporal lobe).

In each case, if the delicate balance between forming new connections and removing connections no longer required is disrupted, Alzheimer pathology may develop. Amyloid PreProtein processing tips away from an alpha-secretase/beta-secretase balance, to produce excess beta-amyloid and resultant free-radicals. Tau is excessively phosphorylated to the point that it forms neurofilaments, and then neurofibrillary tangles.

The neurofilaments appear to clog dendrite segments (Ashford et al., 1998), which leads to amputation of the distal portions of dendritic trees, large scale losses of synapses, and the increase of CSF tau. These late changes correspond with the dementia severity associated with Alzheimer's disease (Ashford et al., 2001 for a discussion of modeling of dementia severity.)

A central factor in Alzheimer's disease is ApolipoProteinE, which is produced by glial cells and accounts for at least 50% of the Alzheimer's disease that occurs between 60 - 80 years of age.

APOE plays a central role in cerebral cholesterol transport. Recent evidence has shown that cholesterol metabolism is involved in neuroplasticity. Epidemiological studies are now implicating cholesterol metabolism in Alzheimer causation. This chain of causation provides yet another buttress to support the neuroplasticity hypothesis of AD.

Additional evidence suggests that cholesterol is involved in Amyloid PreProtein processing, thus linking the APOE alleles to amyloid production, thought to be central to AD causation, and further supporting the role of this mechanism in neuroplasticity and the general neuroplasticity theory of AD ( see Ashford and Mortimer debate position, in press, for full discussion and references [.pdf file]).

Recent evidence supports the hypothesis that acetylcholine, a fundamental neurotransmitter in neuroplasticity, inhibits both senile plaque and neurofibrillary tangle formation (see figure adapted from Fisher, 2000). This hypothesis suggests that drugs which increase acetylcholine function, such as cholinesterase inhibitors, may slow or stop Alzheimer progression.
http://www.alzforum.org/res/for/journal/ashford/default.asp

Still other researchers are testing the idea, gleaned from some population and animal studies, that cholesterol may play a role in Alzheimer's development. In 2002, there will be a large trial to see if taking cholesterol-lowering statin drugs can slow down the progression of clinical signs of the disease in patients with mild to moderate Alzheimer's.
http://www.pbs.org/wnet/brain/episode5/alzheimers/2.html

The relaxation responses of the tissues taken from the patients with hypercholesterolemia to endothelium-dependnent vasoactive agents, acetylcholine (10-9-10-4 mol/L), adenosine (10-9-10-4 mol/L), and high dose bradykinin (10-6-10-5 mol/L) were significantly reduced, as compared to those from the patients with normal blood level of the total cholesterol (n=16).
http://www.asiaandro.com/1008-682X/2/161.htm

Then, the researchers laced some mice's food with a drug to turn off tau production. Afterward, memory improved in those mice.

"The ability to acquire and retain new spatial memories was restored ... and the improvement was related to the suppression of tau and not [the chemical used to suppress tau]," write the researchers.
Surprising Results

The mice's memory recovery was "surprising," write the researchers.
When tau production was curbed, the mice already had "abundant" brain tangles, had lost a significant amount of brain weight, and had lost brain cells, the researchers write.

"Thus, neurofibrillary tangles are not sufficient to cause cognitive decline or neuronal [brain cell] death in this model," write Ashe and colleagues.

SOURCES: SantaCruz, K. Science, July 15, 2005; vol 309: pp 476-481. News release, University of Minnesota. News release, Science.
J Alzheimers Dis. 2004 Dec;6(6):639-649.
Borrelia burgdorferi persists in the brain in chronic lyme
neuroborreliosis and may be associated with Alzheimer disease.

Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J,
Paster BJ.
University Institute of Pathology, Division of Neuropathology, University Medical
School (CHUV), 1011, Lausanne, Switzerland. and University of British Columbia,
Department of Psychiatry, Kinsmen Laboratory of Neurological Research, Vancouver,
B.C. V6T 1Z3, Canada.

The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A
number of contributing factors have been postulated, including infection.
It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition.
PMID: 15665404

In the new study, scientists tested participants' blood. The researchers spotted a difference in immune system cells called macrophages.
"Macrophages are the janitors of the innate immune system, gobbling up waste products in the brain and throughout the body," says researcher Milan Fiala, MD, in a news release. Fiala works in the medical school of the University of California Los Angeles (UCLA), as well as the Greater Los Angeles VA Medical Center.

Participants' macrophages took a test-tube challenge: Clear away amyloid-beta, a building block of Alzheimer's-related brain plaque. Macrophages from healthy participants were up to the task, but those from Alzheimer's patients couldn't clean up adequately. Other parts of the immune system may have to step in to get the job done, say the researchers.
Searching for Solutions

"If further study shows that this defective macrophage function is present in most Alzheimer's disease patients, new hormonal or immune-boosting approaches may offer new approaches to treating the disease," says Fiala.

Curcumin has shown potential against Alzheimer's diseaseCurcumin has shown potential against Alzheimer's disease and cancer in other experiments on mice.

SOURCES: Fiala, M. Journal of Alzheimer's Disease, June 10, 2005. WebMD Medical Reference from Healthwise: "Alzheimer's Disease -- Topic Overview." Alzheimer's Association, "About Alzheimer's -- Statistics About Alzheimer's Disease." News release, UCLA. WebMD Medical News: "Curry Spice May Fight Alzheimer's Disease." WebMD Medical News: "Curry Spice May Curb Breast Cancer's Spread."

Healthy people's immune systems produce antibodies that can get rid of at least some of the beta-amyloid that floats in everyone's bodies. But older people produce one-third fewer antibodies against the protein than younger people do, said Dr. Marc Weksler of the Weill Medical College of Cornell University.

Immune globulin is a cocktail of antibodies culled from blood donors and given intravenously to treat a variety of immune-related diseases. The question is whether giving IVIG to Alzheimer's patients might act as a sponge to soak up extra beta-amyloid.

Weksler gave eight people with mild to moderate Alzheimer's six months of IVIG therapy. The amount of beta-amyloid in their cerebral spinal fluid - a measure of how much reaches the brain - dropped about 45 percent. Cognitive tests suggest the patients may have stabilized during treatment, although Weksler stressed that it's impossible to tell from such a small study that had no comparison group.
-------------
� Chronic nicotine exposure increases tangles in a mouse model of Alzheimer's disease -UCI researchers have determined that chronic nicotine exposure worsens some Alzheimer's-related brain abnormalities, contradicting the common belief that nicotine can actually be used to treat the disease.

� In the latest online edition of the Proceedings of the National Academy of Sciences, the researchers report that chronic nicotine exposure increases neurofibrillary tangles - the bundles of fibers that are one of the two neuropathological hallmarks of the disease, the other being clump-like plaques.

� Alzheimer's disease is a slow, progressive disease and the most common cause of dementia among the elderly in the United States, affecting 4.5-5 million adults - 10 times more than those affected by Parkinson's disease.

� The disease is marked by the accumulation of two distinct brain lesions - beta-amyloid plaques and neurofibrillary tangles - which accumulate in specific brain regions critical to learning and memory.

� "In earlier work, we showed that plaques can induce tangles," said Salvatore Oddo, graduate student in the School of Biological Sciences' Department of Neurobiology and Behavior, and the first author of the paper.

� The researchers found that chronic nicotine exposure increased the tangles while having no significant effect on the plaques.

� "In contrast to previous reports that nicotine has some marginally positive effects, our latest findings suggest that chronic nicotine exposure may actually be detrimental, enhancing certain Alzheimer's disease brain pathologies," said Frank LaFerla, principal investigator of the research project, associate professor of neurobiology and behavior, and co-director of the UCI Institute for Brain Aging and Dementia.

� Starting with mild memory problems and ending with severe brain damage, Alzheimer's usually begins after the age of 60, the risk increasing with age.
Source:
http://www.medicalnewstoday.com/medicalnews.php?newsid=19787

(First smoking was good for preventing, then bad...so much for trying to follow research, hey?)

Bb follows the cholesterol pathway...

Gram-positive cocci, and the spirochete Borrelia burgdorferi employ exclusively the mevalonate pathway (Rohmer 1999; Kim et al. 2000; Wilding et al. 2000a, b).

Synonyms: isoprenoid pathway
The mevalonate pathway is responsible for the biosynthesis of cholesterol, other sterols, and isoprenoid lipids.
http://lifeextensionvitamins.com/ospa2.html

Statin drugs and Mg shut off this pathway by INactivating an enzyme in the liver at step #1.

AND...Mg is capable of DNA REPAIR...it ALSO controls the enzyme PFK which Bb is "dependent on". This enzyme is "rate limiting" for glycolysis. Bb loves sugar.

[This message has been edited by Marnie (edited 20 July 2005).]
 

04/05/2005- Scientists have found genetic proof that vitamin E can help protect against Alzheimer's disease, said DSM yesterday.

This most recent study was published in Nutritional Neuroscience (February 2005, 8;21-29).
http://www.nutraingredients.com/news/printNewsBis.asp?id=59811

Vitamin A and E work together and are potent ***antioxidants. See my post:
http://flash.lymenet.org/ubb/Forum1/HTML/036099.html

 

Not research but does give pause to believe there could be a connection here.

Plaque show with a Spect Scan in the brains of those diagnosed with neuropsychiatric Lyme disease shows up in the brains of Alzheimer's patients.

SandiB
 

Which in any event is not to say that Alzheimers disease is not bacterial in some/all cases. In fact it could very well be borrelial. Alan MacDonald, Judit Miklossy, and R McLaughlin wrote the key papers on this possibility.