Showing posts with label beta-amyloid. Show all posts
Showing posts with label beta-amyloid. Show all posts

Saturday, September 20, 2008

MEDICAL NEWS: New Pathways Between Memory Loss, Alzheimer's

(previously published here at www.thebulletin.us)

Mild cognitive impairment (MCI) is a stage between normal aging and Alzheimer's earliest stages. Understanding how it goes from mild thought problems to dementia could be key to figuring out how to prevent Alzheimer's. The following details of some of the latest research can give you an idea of the importance of aiming early.


Understanding Risk Factors

According to a Mayo Clinic report, the MCI rate increases with age and is higher in men, who are almost twice as likely to develop the condition than women. Although previous studies show women at higher risk of dementia and Alzheimer's, women generally outlive men, perhaps surviving long enough for their conditions to progress.

According to Dr. B. Brent Simmons, assistant professor and head of Temple University Hospital's Senior Care Specialists section of geriatrics, the higher rates of heart disease in men might also affect their chances of getting vascular dementia.

This study collected data from 1,786 people aged 70 to 89 and found that after a year, about 3.5 percent of 70- to 79-year-olds and 7.2 percent of 80- to 89-year-olds become afflicted with it. Overall, the growth rate of new MCI cases in the elderly population is at 5 percent per year - higher than anticipated.


Drug Development

In research by New York's Mt. Sinai School of Medicine, the brains of 124 diabetics taking medication (insulin and other glucose-lowering drugs) had up to 80 percent less beta-amyloid plaque compared to other diabetics and 124 non-diabetics. Beta-amyloid protein clumps in and around the brain, forming plaque that inhibits and destroys neurons necessary for daily functions and memory.

However, even if a combination of insulin and oral anti-diabetes medications may prevent Alzheimer's-related factors, they cannot be prescribed for non-diabetics. Hopefully, though, brain pathways such as insulin signaling could be used in developing new treatment methods.

Besides plaque, Alzheimer's indicators include unusual changes to a protein called tau. A yearlong trial at Duke University Medical Center tested a promising new drug - a nasal spray called AL-108 - on 144 patients with MCI, between ages 55 and 85, and saw a 62.4 percent improvement in memory ability.

Patients took several tests that measured memory ability before and after medication. The tests measured short-term visual, verbal and auditory working memory, functions that deteriorate throughout the progression of Alzheimer's.

Although this drug doesn't cure Alzheimer's, it showed that attacking the protein tangles does work, stabilizing some of the progress of dementia.


Getting It Before It Starts

Instead of just treating symptoms, researchers at the University of Pennsylvania School of Medicine are trying to stop it before it starts, by finding chemical and biological markers of these conditions.

Since Alzheimer's is a disease measured by analyzing symptoms, the goal of the first investigation was, according to its lead researcher, Dr. Leslie Shaw, "to determine if we could detect Alzheimer's disease pathology before a patient went on to have full blown dementia and memory disorders."

The research focused on measuring levels of cerebral spinal fluid (CSF) and establishing benchmark concentration levels of biological indicators for normal, mildly cognitively impaired, and Alzheimer's individuals.

The differences between the baseline levels of three Alzheimer's-associated proteins were significant enough to speed up drug development efforts of biological compounds that can fix these differences.

The second Penn study uses MRI scans to detect abnormal structural changes linked to MCI in the brains of healthy elderly. Radiology professor Christos Davatzikos, Ph.D. and his colleagues monitored these slight physical changes to the brain successfully might provide a way to alert patients and doctors to brain deterioration and memory decline early enough to prepare or begin treatment.

With around 18 percent of 400 patients converting to Alzheimer's a year, this study is ongoing, and doctors are able to "study the progression as it's happening ... at a rate large enough to make our tests reliable or not with sufficiently large number of study subjects," said Dr. Shaw, who is also the director of Penn's ADNI Biomarker Core Lab.

Collaboration is key for all involved, and as Dr. Shaw noted, "the earlier we can detect the disease reliably with confidence, the earlier we can institute and monitor treatment such as diet, exercise, adjusted sleep patterns and having a social life, along with doctor visits, to delay and stop the disease."

The MRI-based study used images from the Baltimore Longitudinal Study of Aging (BLSA) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) and was funded by the National Institute on Aging and the Institute for the Study of Aging.

Dr. Shaw's research was funded by the Alzheimer's Disease Neuroimaging Initiative via the National Institutes of Health.


Heather J. Chin can be reached at hchin@thebulletin.us.

©The Evening Bulletin 2008

Saturday, June 28, 2008

An Alzheimer's Minibreakthrough

(previously published at www.thebulletin.us)


The dementia and loss of mental faculties resulting from Alzheimer's disease has long been recognized, but the exact cause has remained elusive, until perhaps now.

New research suggests that one form of beta-amyloid protein - which clumps around an afflicted brain's neurons and forms plaque that inhibits and destroys neurons needed for daily functions and memories - causes symptoms of Alzheimer's.

Previous research had been unable to determine whether the beta-amyloid plaque was a cause or a side effect of Alzheimer's disease.

In the new study, researchers caused Alzheimer's symptoms of impaired memory function in rats by injecting them with a two-molecule soluble form of beta-amyloid protein.

One-molecule and three-molecule forms of both soluble and insoluble proteins did not trigger illness in the rats, which researchers say may explain why some people with beta-amyloid plaque don't exhibit such symptoms.

Dr. Ganesh M. Shankar and Dr. Dennis J. Selkoe of Harvard Medical School published their findings in Sunday's online edition of the journal Nature Medicine. In the report, they noted that when studies were also conducted on mice, the brain cell density was reduced by 47 percent, and affected the synapses, or connections between cells that are necessary for cell communication.

Beta-amyloid extracts were taken from the brains of people who had donated their bodies to medical research.

This is the first time that research has showed the effect of a particular type of beta-amyloid in the brain, said Dr. Marcello Morrison-Bogorad, director of the division of neuroscience at the National Institute on Aging, to the Associated Press.

He added that the revelation that only one of three types of the proteins had a damaging effect on the brain is important because doctors have long wondered why they find some plaque-covered brains in autopsy that belong to a person who didn't have Alzheimer's.

"A lot of work needs to be done," stated Dr. Morrison-Bogorad, as to why one protein has a damaging effect and not others. "Nature keeps sending us down paths that look straight at the beginning, but there are a lot of curves before we get to the end."

The Harvard study was funded by the National Institute on Aging, Science Foundation Ireland, Wellcome Trust, the McKnight and Ellison foundations and the Lefler Small Grant Fund.

In a separate study out of the Feinstein Institute of Medical Research in New York, Dr. Yousef al-Abed, chief of medicinal chemistry, and his colleagues Michael Bacher and Richard Dodel of Marburg University in Germany created and tested an experimental drug that they say might neutralize or reduce the effects of the beta-amyloid plaques in the patient's brain.

Published in the Journal of Experimental Medicine, the study's results describe an experimental medicine, CNI-1493, already being tested as a medicine for the bowel affliction called Crohn's disease, that targets and transforms amyloid in the brain so that it does not clump and form plaque and also loses its toxicity.

Their results show a 70 to 85 percent reduction of amyloid buildup in the cortex and the hippocampus - the two areas of the brain most affected in Alzheimer's patients and which affect memory, attention, perceptual awareness, language, consciousness and the regulation of emotion.

Heather Chin can be reached at heather.jean.chin@gmail.com

©The Evening Bulletin 2008