Posts tagged beta amyloid
Articles and news from the latest research reports.
Surgical menopause may prime brain for stroke, Alzheimer’s
Women who abruptly and prematurely lose estrogen from surgical menopause have a two-fold increase in cognitive decline and dementia.
"This is what the clinical studies indicate and our animal studies looking at the underlying mechanisms back this up," said Brann, corresponding author of the study in the journal Brain. “We wanted to find out why that is occurring. We suspect it’s due to the premature loss of estrogen.”
In an effort to mimic what occurs in women, Brann and his colleagues looked at rats 10 weeks after removal of their estrogen-producing ovaries that were either immediately started on low-dose estrogen therapy, started therapy 10 weeks later or never given estrogen.
When the researchers caused a stroke-like event in the brain’s hippocampus, a center of learning and memory, they found the rodents treated late or not at all experienced more brain damage, specifically to a region of the hippocampus called CA3 that is normally stroke-resistant.
To make matters worse, untreated or late-treated rats also began an abnormal, robust production of Alzheimer’s disease-related proteins in the CA3 region, even becoming hypersensitive to one of the most toxic of the beta amyloid proteins that are a hallmark of Alzheimer’s.
Both problems appear associated with the increased production of free radicals in the brain. In fact, when the researchers blocked the excessive production, heightened stroke sensitivity and brain cell death in the CA3 region were reduced.
Interestingly the brain’s increased sensitivity to stressors such as inadequate oxygen was gender specific, Brann said. Removing testes in male rats, didn’t affect stroke size or damage.
Although exactly how it works is unknown, estrogen appears to help protect younger females from problems such as stroke and heart attack. Their risks of the maladies increase after menopause to about the same as males. Follow up studies are needed to see if estrogen therapy also reduces sensitivity to the beta amyloid protein in the CA3 region, as they expect, Brann noted.
Brann earlier showed that prolonged estrogen deprivation in aging rats dramatically reduces the number of brain receptors for the hormone as well as its ability to prevent strokes. Damage was forestalled if estrogen replacement was started shortly after hormone levels drop, according to the 2011 study in the journal Proceedings of the National Academy of Sciences.
The surprising results of the much-publicized Women’s Health Initiative – a 12-year study of 161,808 women ages 50-79 – found hormone therapy generally increased rather than decreased stroke risk as well as other health problems. Critics said one problem with the study was that many of the women, like Brann’s aged rats, had gone years without hormone replacement, bolstering the case that timing is everything.
(Source: eurekalert.org)
Green tea extract interferes with the formation of amyloid plaques in Alzheimer’s disease
Researchers at the University of Michigan have found a new potential benefit of a molecule in green tea: preventing the misfolding of specific proteins in the brain.
The aggregation of these proteins, called metal-associated amyloids, is associated with Alzheimer’s disease and other neurodegenerative conditions.
A paper published recently in the Proceedings of the National Academy of Sciences explained how Life Sciences Institute faculty member Mi Hee Lim and an interdisciplinary team of researchers used green tea extract to control the generation of metal-associated amyloid-β aggregates associated with Alzheimer’s disease in the lab.
The specific molecule in green tea, (—)-epigallocatechin-3-gallate, also known as EGCG, prevented aggregate formation and broke down existing aggregate structures in the proteins that contained metals—specifically copper, iron and zinc.
"A lot of people are very excited about this molecule," said Lim, noting that the EGCG and other flavonoids in natural products have long been established as powerful antioxidants. "We used a multidisciplinary approach. This is the first example of structure-centric, multidisciplinary investigations by three principal investigators with three different areas of expertise."
The research team included chemists, biochemists and biophysicists.
While many researchers are investigating small molecules and metal-associated amyloids, most are looking from a limited perspective, said Lim, assistant professor of chemistry and research assistant professor at the Life Sciences Institute, where her lab is located and her research is conducted.
"But we believe you have to have a lot of approaches working together, because the brain is very complex," she said.
The PNAS paper was a starting point, Lim said, and her team’s next step is to “tweak” the molecule and then test its ability to interfere with plaque formation in fruit flies.
"We want to modify them for the brain, specifically to interfere with the plaques associated with Alzheimer’s," she said.
Lim plans to collaborate with Bing Ye, a neurobiologist in the LSI. Together, the researchers will test the new molecule’s power to inhibit potential toxicity of aggregates containing proteins and metals in fruit flies.
Plaque Build-Up in Your Brain May Be More Harmful Than Having Alzheimer’s Gene
A new study shows that having a high amount of beta amyloid or “plaques” in the brain associated with Alzheimer’s disease may cause steeper memory decline in mentally healthy older people than does having the APOE ɛ4 allele, also associated with the disease. The study is published in the October 16, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.
“Our results show that plaques may be a more important factor in determining which people are at greater risk for cognitive impairment or other memory diseases such as Alzheimer’s disease,” said study author Yen Ying Lim, MPsych, with the University of Melbourne in Victoria, Australia. “Unfortunately, testing for the APOE genotype is easier and much less costly than conducting amyloid imaging.”
Image credit: PASIEKA/SCIENCE PHOTO LIBRARY
Alzheimer’s villain cures multiple sclerosis in mice
A notorious biochemical villain has just revealed its heroic side. Beta-amyloid, a misfolded protein fragment blamed for killing brain cells in Alzheimer’s disease, has reversed the symptoms of mice suffering from the rodent equivalent of multiple sclerosis (MS).
MS occurs when the immune system mistakenly attacks the fatty myelin sheaths around nerve fibres that serve as electrical insulation. Without this insulation, nervous impulses falter, leading to physical and cognitive problems. Myelin increases the speed at which electrical impulses travel around the body.
As it is destroyed, nerve communication falters, leading to physical and cognitive problems. Lawrence Steinman of Stanford University in California had expected amyloid-beta to exacerbate this damage, given that it is toxic to neurons and builds up where myelin sheaths are being destroyed.