Vidyya Medical News Service
Volume 6 Issue 300 Published - 14:00 UTC 08:00 EST 26-Oct-2004 Next Update - 14:00 UTC 08:00 EST 27-Oct-2004
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Researchers identify brain protein that halts progression of Alzheimer's

Researchers have identified a protein in the brain that halts the progression of Alzheimer's disease in human brain tissue. The protein, known as "transthyretin," protects brain cells from gradual deterioration by blocking another toxic protein that contributes to the disease process.

The National Institute of Environmental Health Sciences, a component of the National Institutes of Health, provided $1.25 million to University of Wisconsin-Madison scientists for the transthyretin study. The scientists will present their findings October 26 at the 34th annual meeting of the Society for Neuroscience in San Diego, Calif.

"The results of this study are promising," said Kenneth Olden, Ph.D., director of the NIEHS. "More studies are needed to understand how transthyretin can be used in treating Alzheimer's patients."

Alzheimer's disease progresses when a toxic protein, known as "beta-amyloid," attacks the brain's nerve cells involved in learning and memory. The beta-amyloid creates sticky plaques and tangles that gradually disable nerve cells, producing memory loss. Transthyretin appears to protect brain cells by intercepting the beta-amyloid and preventing it from interacting with the brain tissue.

"Based on the results of animal studies, we know that the disease process depends in large part on the delicate balance between the 'good' transthyretin protein and the 'bad' beta-amyloid protein," says Dr. Jeff Johnson, associate professor at the University of Wisconsin's School of Pharmacy and lead author on the study. "In Alzheimer's patients, the 'bad' proteins significantly outnumber the 'good' proteins."

Johnson discovered the effect of transthyretin while studying mice genetically engineered with defective genes taken from human patients with early-onset Alzheimer's disease. As expected, the defective genes produced mice with higher-than-normal levels of the toxic beta-amyloid protein. These mice did not, however, exhibit symptoms of Alzheimer's disease.

"We have a mouse whose brain is bathing in toxic beta-amyloid without exhibiting disease symptoms," says Johnson. "We were all asking the same question – Why aren't these nerve cells dying?"

Dr. Thor Stein, a researcher in Johnson's laboratory and first author of the study, then analyzed the brains of mice and noticed that the levels of transthyretin had increased dramatically. When Stein treated the mouse brain with an antibody that prevented transthyretin from reacting with the beta-amyloid protein, the mice showed brain cell death. "We concluded that the transthyretin must have protected the brain cells from the toxic effects of the beta-amyloid," says Johnson.

Test tube studies with cultured brain cells from human cortex support the findings. When Stein treated human brain cells with the transthyretin protein, then exposed the cells to the toxic beta-amyloid, the brain cell death was minimal. "Now that we have demonstrated that this protective mechanism is relevant to humans, we can start to identify strategies to slow nerve degeneration in Alzheimer's patients," says Johnson.

According to Johnson, this would involve developing drugs that would boost the transthyretin within the brain or methods depositing transthyretin into the brain. "Hopefully this research will inspire a new approach to the treatment of Alzheimer's, one focused on preventing the loss of the brain cells instead of treating the resulting symptoms."

Johnson foresees a time when family members with a genetic predisposition to Alzheimer's disease could take a yet-undeveloped drug to increase transthyretin protein and prevent the disease from developing. Theoretically, the drug also could be given in the early stages of Alzheimer's to stop progression of the disease, preserving a higher level of cognitive function in patients.

The transthyretin discovery will likely impact the screening of environmental chemicals for their potential role in causing or exacerbating Alzheimer's disease. "Researchers could develop tests that determine whether a particular chemical or agent in the environment is able to shift the delicate balance between the 'good' and 'bad' proteins," notes Johnson. "This would allow scientists to establish definitive links between environmental exposures and Alzheimer's disease pathology."

Additional Vidyya Resources:

   Alzheimer's Disease  
   Alzheimer's Disease And Dementia: Reminyl (Galantamine Hydrobromide)  
   Alzheimer's Disease Fact Sheet  
   Alzheimer's disease genetics fact sheet   
   Alzheimer's disease - Unraveling the mystery  
   Forgetfulness: It’s Not Always What You Think  
   Alzheimer's Disease: Unraveling the Mystery  
   New Fronts in Alzheimer's Research  
   Alzheimer's Disease Info: Questions to Ask the Doctor (Administration on Aging)   
   Mild Cognitive Impairment: Possible Predictor of Alzheimer's (Mayo Foundation for Medical Education and Research)  
   Agitation and Alzheimer's Disease (Alzheimer's Association) - Links to PDF File   
   Depression and Alzheimer's Disease (American Academy of Family Physicians)   
   Sleep Changes in Alzheimer's Disease (Alzheimer's Association) - Links to PDF File   
   Alzheimer's Disease Medications (National Institute on Aging)  
   Coping with Changes in Daily Life (Alzheimer's Association)   
   Helping Your Family and Friends (Alzheimer's Association)   
   Making Job Decisions (Alzheimer's Association)   
   Aluminum and Alzheimer's Disease (Alzheimer's Association) - Links to PDF File  
   Choosing Health Care Providers and Facilities (Alzheimer's Association)   
   Financial Matters for Alzheimer's Care (Alzheimer's Association)  
   Alzheimer's Disease Education and Referral (ADEAR) Center (National Institute on Aging)   
   Alzheimer's Association  
   Administration on Aging   
   Fisher Center for Alzheimer's Research Foundation   

News Articles:

   Alzheimer's: Searching for a cure -19-August-2003   
   Antibiotic therapy for Alzheimer's? -10-October-2003   
   Anti-inflammatory drugs lower risk of Alzheimer's -18-July-2003  
   Brain plaques in Alzheimer’s disease linked to eye disease -11-May-2003  
   Can vitamins slow the progression of Alzheimer’s disease? -16-March-2003  
   Drug Improves Brain Structure in Alzheimer's Patients -03-November-2003  
   Enzyme helps guard against Alzheimer's disease -31-July-2003  
   Enzyme reponsible for Alzheimer's plaques blocked by lithium. -22-May-2003  
   FDA approves memantine (Namenda) for Alzheimer's disease -18-October-2003   
   Findings reported in February Archives of Neurology provide new insights on Alzheimer’s disease -19-February-2003   
   First study of Alzheimer's caregivers and end-of-life cites both remarkable resilience, need for support -14-November-2003  
   Information from the FDA: Alzheimer's --- Searching for a cure -22-July-2003  
   Leisure activity may reduce risk of Alzheimer's -21-October-2003  
   Neuroscientists pinpoint midlife crisis in brain circuitry as key to brain aging and onset of Alzheimer's later in life -30-December-2003  
   A new molecular culprit for type II diabetes, Alzheimer's and Parkinson's -22-October-2003   
   New studies in mice suggest ways to clear damaging Alzheimer’s amyloid plaques -26-May-2003   
   Rush researchers find effects of Alzheimer's disease may be influenced by education -25-June-2003  
   Searching for 1,000 families with multiple members with Alzheimer's disease -26-July-2003  
   Stroke may increase risk of Alzheimer disease -16-December-2003  
   Study boosts confidence in potential screening tool for Alzheimer's disease Lifestyle changes effective in lowering blood pressure -24-April-2003   
   Study boosts confidence in potential screening tool for Alzheimer's disease -02-May-2003  
   Study shows people with Alzheimer's can benefit from exercise combined with caregiver training -15-October-2003  
   Study suggests dramatically rising numbers of people with Alzheimer’s disease -19-August-2003   
   Synthetic marijuana reduces agitation in patients with Alzheimer’s -16-November-2003  
   3-D images show how Alzheimer's engulfs brain -09-February-2003   
   Two new studies showed Alzheimer’s disease treatment beneficial in other memory-related conditions -06-April-2003  
   UCLA researcher discovers the role of common painkillers in protecting against Alzheimer's disease -13-March-2003  
   Unusual form of memory loss often confused for Alzheimer's disease -20-October-2003  
   Additional information: Low free testosterone levels linked to Alzheimer’s disease in older men -30-January-2004  
   Alzheimer’s Association statement on a study of clioquinol targeting Aß amyloid deposition and toxicity in alzheimer’s disease from Archives Of Neurology, December 2003 -05-January-2004   
   Brain cell death in Alzheimer’s disease linked to protein accumulation and insulin biochemistry -22-June-2004  
   Brightly colored cups, plates spur food, beverage consumption in advanced Alzheimer's disease -25-September-2004  
   Diabetes linked to increased risk of Alzheimer's in long-term study -22-May-2004  
   Diagnosticians would do well to raise the bar when testing high-functioning people for pre-clinical signs of Alzheimer's disease -05-January-2004  
   Immunoglobulin therapy for Alzheimer's? -18-September-2004  
   The mentally-demanding job and development of Alzheimer's disease -10-August-2004  
   New animal model for Alzheimer vaccine -07-March-2004  
   New research may explain how fats damage neurons in Alzheimer's patients and how diet, hormones and exercise might delay disease onset -16-February-2004  
   New study supports use of PET scans in early diagnosis of Alzheimer’s disease -12-March-2004  
   No clear-cut answers on statins as therapy for Alzheimer's disease -19-July-2004  
   Pharmaceutical "metal binder" could put the breaks on Alzheimer symptoms -05-January-2004  
   Study is another step in determining if curry can protect against Alzheimer's -19-April-2004  
   Study: Distress-prone people more likely to develop Alzheimer's disease -19-January-2004  
   Study identifies predictors of Alzheimer's disease longevity -8-April-2004  
   Study suggests antipsychotics do not raise risk of stroke in Alzheimer's patients -23-July-2004  
   TANGO towards faster prognosis of Alzheimer's and Parkinson's diseases? -14-September-2004  
   Two proteins may help prevent Alzheimer's brain plaques -22-January-2004  
   Two studies examine relationship between Alzheimer's disease and testosterone -27-January-2004   
   2001-2002 Progress report on Alzheimer's disease -19-January-2004  
   Vitamin supplement use may reduce effects of Alzheimer's disease -20-January-2004  
   When should early-Alzheimer's patients stop driving? Visuospatial tests best predictors of driving skill -26-January-2004   

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