Alzheimer's May Vary, Brain to Brain

Differences in plaque-forming structures in the brains of Alzheimer's patients may offer clues to why the disease can progress more rapidly or be less severe in some people, a new study suggests.

The research could spur the development of new imaging agents that highlight specific structures in the brain -- called beta-amyloid fibrils -- improving the reliability and specificity of diagnosis, according to Robert Tycko.  "Variations in disease may have a structural basis and be due to differences in the molecular structure of the fibrils," said Tycko, a senior investigator with the intramural research program of the U.S. National Institutes of Health.

The study represents an important advance in Alzheimer's research, an expert not involved with the study noted.

Beta-amyloid fibrils are responsible for the amyloid plaques seen in Alzheimer's disease, the most common form of dementia. Alzheimer's is the sixth leading cause of death in the United States and more than 5 million Americans have the disease, according to the Alzheimer's Association. For the research, the scientists took tissue from the brains of two deceased female Alzheimer's patients with different signs and symptoms of the disease. They extracted beta-amyloid from the tissue and used it as "seeds" to grow beta-amyloid fibrils. The investigators found that the same "seeds" -- the amino acid sequence -- could assemble into different molecular structures.

Using nuclear magnetic resonance and electron microscopy to visualize the beta-amyloid fibrils in the patients' brain tissue, the scientists discovered correlations between variations in the disease and differences in molecular structure.

"There are at least two different varieties [of amyloid structure] in Alzheimer's disease," Tycko said. "And certain fibril structures may be more likely than others to cause the disease."

Tycko explained that while the research team was able to determine that there are at least two structural varieties of Alzheimer's disease, they were unable to prove that there are correlations between variations in disease and molecular structure.

He said he hopes that the research will eventually lead to the ability to tell someone with memory loss whether or not the problem is likely to lead to a serious or fast-moving form of Alzheimer's.

One expert not involved with the research called the discovery a "technical tour de force."

"The research is a huge step forward," said Terrence Town, a professor of physiology and biophysics at the Keck School of Medicine at the University of Southern California. "They have accomplished something we have been trying to do for a decade."

For years, researchers have been focusing on something smaller than a fibril, called an oligomer, considered to be especially toxic to the brain, Town explained. "Now this paper is drawing attention to something different: fibrils."

The findings will help researchers focus on the fibrils, ideally working toward developing ways to identify and diagnose people in the earliest stages of the disease, Town said.

Popular Asian spice can cure Alzheimer's disease

Nature is full of various herbs and spices that protect against disease and even treat and cure it. And according to Chris Kilham, turmeric root -- also known in its extract form as curcumin -- is one such powerful spice that appears to both prevent the onset of Alzheimer's disease and even cure it.

"People who develop Alzheimer's disease get a sticky plaque in the brain called amyloid beta," explained Kilham to Dr. Manny Alvarez in a recent Fox News interview. Such plaques either develop as a result of Alzheimer's, or they are the direct cause of it. But either way, they are directly related to the degenerative process.

However studies show that turmeric actually eliminates these plaques, both when they are first starting to form and even during the late stages of their advancement.

"What we have in turmeric is something that appears to inhibit the development of Alzheimer's disease…and actually help to reduce the occurrence of plaque in the brain if you have it," noted Kilham. "We know in animal studies, when animals actually have amyloid beta plaque in their brains and they're given turmeric root…that plaque is reduced."

Observational studies have also shown that people groups who eat large amounts of turmeric virtually never get Alzheimer's.

"In countries where people consume a lot of [turmeric], there's a very low incidence of Alzheimer's disease," emphasized Kilham. "In India and Southeast Asia, it's a rare disease. And [in the U.S.] it's very, very common."

According to Kilham, drug companies are hard at work trying to develop drug versions of turmeric, but he recommends eating real turmeric whenever possible, and taking turmeric extract supplements if eating the spice in food is not an option.

"A challenge that we face is that drug companies…can't patent turmeric root," he said. "So they will continue to try to develop something else. [But] eating turmeric, eating its extracts…appears to be protective against one of the most horrific and debilitating diseases we know."

A Potential New Strategy to Address Dementia

Alzheimer's disease affects millions of people worldwide. As a result of an increase in life expectancy, the number of patients with dementia is expected to increase dramatically. Due to the lack of effective treatments that can slow down or reverse the progression of AD, preventive measures to lower the prevalence rate of AD by means of managing potential or actual risk factors is a reasonable clinical strategy. In this respect, identifying treatable factors which are able to promote cognitive deterioration would have important practical implications.

In a recent study, a research group from the Neurological Clinic of Università Politecnica delle Marche, Ancona, Italy described an interesting association between the presence of sleep-disordered breathing and AD. 

The study, coordinated by Mauro Silvestrini and Leandro Provinciali with Laura Buratti as principal investigator, found that a significant percentage of AD patients suffer from Obstructive Sleep Apnea Syndrome (OSAS), a common but largely underdiagnosed respiratory disorder that causes people to temporarily stop breathing during their sleep. Most importantly, the presence of this nocturnal disorder leads to unfavorable changes in cerebral blood flow that are well recognized promoters of cognitive decline onset and progression. Based on these findings, detecting and treating OSAS before it becomes severe enough to cause irreversible effects on cerebral circulation should be considered a very promising clinical approach for AD.

Newly Identified Antibodies Effectively Treat Alzheimer's-Like Disease in Mice

Alzheimer's disease is characterized by the accumulation of particular toxic proteins in the brain that are believed to underlie the cognitive decline in patients.

A new study conducted in mice suggests that newly identified antibody treatments can prevent the accumulation of one of these of these toxic components, called tau proteins. The findings suggest that these antibodies may provide a basis for a promising therapy for patients with Alzheimer's disease and other neurodegenerative disorders.

In the brains of patients with Alzheimer's disease and several other neurodegenerative conditions, tau proteins aggregate together and become tangled, a process that interferes with the brain's function and can cause many of the symptoms that patients experience.

Investigators led by Drs. David Holtzman and Marc Diamond of Washington University School of Medicine in St. Louis conducted studies in mice to reveal potential treatments to block this process. "We have identified anti-tau antibodies that can strongly reduce tau pathology, decrease tau accumulation, and improve cognitive function in a mouse model of a neurodegenerative disease called frontotemporal dementia," explains Dr. Holtzman. "Similar tau pathology is seen in Alzheimer's disease, implying that this could be an exciting treatment for a large number of patients."

To make their discovery, the researchers used a screening technique to sift through numerous antibodies to isolate those that could prevent uptake of tau aggregates by cells and block subsequent intracellular tau aggregation. They then infused three anti-tau antibodies into the brains of diseased mice over three months. While the anti-tau antibodies markedly reduced tau accumulation and improved cognitive deficits in the animals, a control antibody not directed against tau had no beneficial effects. The findings further support work suggesting that spread of tau aggregates between cells is an important mechanism underlying tau-mediated disease.

This study, which is the first to report the effects of direct infusion of anti-tau antibodies into the brain, has important implications for the design of therapeutic antibodies for patients struggling with some of the most debilitating brain diseases. "In addition to the near-term implications for passive vaccination of patients, it suggests that therapies designed to target propagation of protein aggregation between cells could be very effective," says Dr. Diamond.