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Tuesday, February 23, 2016

The Immune System May Play a Larger Role in AD Than Previously Thought


Dear Readers,

According to a new study out of UC Irvine researchers found that immune cells that normally help us fight off various infections may also fight off AD. Study results appeared in the February 16,2016 online issue of the Proceedings of the National Academy of Sciences.

Microglia, immune cells that dwell in the brain, attempt to clear sticky amyloid plaques. However in AD, the effort is an uphill battle. Many studies have looked at the role microglia plays in AD, but very few researchers have explored whether another set of immune cells called T-cells and B-cells that live outside the brain could play a part in autoimmune diseases that might also affect AD.

To test this theory Mathew Blurton-Jones, assistant professor of neurobiology and behavior, and doctoral student Samuel Marsh bred genetically modified mice to develop AD. While this is common in animal research, their mice lacked three key immune cell types, T-cells, B-cells and NK-cells.

During autopsy they compared the immune-deficient mice brains to other mice bred to develop AD, but with intact immune systems. They found a better than twofold increase in beta-amyloid accumulation in the mice lacking the three significant immune cell types. Furthermore they found that AD mice with the intact immune systems that harbored antibodies, which are made by B-cells, accumulated in the brain, showing an association with microglia that resulted in improving beta-amyloid clearance.

To further confirm the value of this relationship between immune cells in the blood and those in the brain, the researchers transplanted healthy bone marrow stem cells into the immune-deficient Alzheimer’s mice. Since T-, B- and NK-cells develop from bone marrow stem cells, this transplantation led to a reconstitution of the missing immune cells. This allowed the B-cells to produce antibodies that once again reached the brain and aided microglia in eliminating the beta-amyloid.


Thanks for reading,

Jeffree Itrich, M.J., M.S.W
Alzheimer's Disease Cooperative Study
UC San Diego
 
Author: Jeffree Itrich at 3:55 PM 0 Comments

Tuesday, February 09, 2016

Blood Protein Could Be a Biomarker for Alzheimer’s


A discovery by researchers at Tel Aviv University, Technion (Rambam Medical Center), and Harvard University advance the screening and diagnosing Alzheimer’s disease (AD). A new study, published in the Journal of Alzheimer’s Disease, proposes a new biomarker for cognitive aging and AD: activity-dependent neuroprotective protein (ADNP). Levels of ADNP can be easily examined in routine blood tests. The study also found that ADNP levels tested in the blood correlate with higher IQ in healthy older adults.

The research was led by Professor Illana Gozes, the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and former director of the Adams Super Center for Brain Studies at TAU’s Sackler Faculty of Medicine and a member of TAU’s Sagol School of Neuroscience, conducted by TAU PhD student Anna Malishkevich and spearheaded by Dr. Gad Marshall, Dr. Aaron Schultz, and Prof. Reisa Sperling of Harvard University, and Prof. Judith Aharon-Peretz of Rambam Medical Center – The Technion Institute of Technology.

Significant increases in ADNP RNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD. ADNP levels tested in plasma and serum samples, as well as white blood cell RNA levels, differentiated between cognitively normal elderly, MCI, and AD participants.

The researchers analyzed blood samples taken from 42 healthy adults, MCI patients, and AD patients at Rambam Medical Center in Israel. After comparing the ADNP expression in the blood samples, the researchers prepared plasma samples and once again compared the protein levels. Professor Gozes determined that they could detect the biomarker in a routine blood test. Her plans are to take these groundwork findings into clinical trials, to hopefully create a pre-Alzheimer’s test that will help shape potential preventative treatments and to clarify ADNP’s ability to predict cognitive decline and disease progression.

This latest research builds on Professor Gozes’ earlier exploration of neuronal plasticity and nerve cell protection at the molecular, cellular, and system level, and her discovery of unique protein families, including ADNP, associated with cross-communication among neural nerve cells and their support cells.
 
Author: Jeffree Itrich at 3:14 PM 0 Comments

Thursday, February 04, 2016

UCLA Nursing Research Finds Possible Answer to Why Some Develop AD and Others Don’t


Dear Readers,

Alzheimer’s disease affects millions, but there is no cure and no real test for the diagnosis until death, when an examination of the brain can reveal the amyloid plaques that are a telltale characteristic of the disease.

Interestingly, the same plaque deposits have also been found in the brains of people who had no cognitive impairment, which has led scientists to wonder: Why do some develop Alzheimer’s and some do not?

Researchers at the UCLA School of Nursing, led by Professor Karen Gylys, may have just uncovered the answer. Their study, published in the January issue of the American Journal of Pathology, is the first to look at disease progression in the synapses — where brain cells transmit impulses.

The researchers analyzed autopsy tissue samples from different locations of the brains of patients who were considered cognitively normal and those who met the criteria for dementia. Using flow cytometry — a laser-based technology that suspends cells in a stream of fluid and passes them through an electronic detection apparatus — they measured the concentration of two of the known biochemical hallmarks of Alzheimer’s: amyloid beta and p-tau, proteins that when found in high levels in brain fluid are indicative of Alzheimer’s. This allowed the scientists to see large populations of individual synapses — more than 5,000 at a time — versus just two under a microscope.

They found that people with Alzheimer’s had elevated concentrations of synaptic soluble amyloid-beta oligomers – smaller clusters of amyloid-beta that are toxic to brain cells. These oligomers are believed to affect the synapses, making it harder for the brain to form new memories and recall old ones.

“Being able to look at human synapses has almost been impossible,” Gylys said. “They are difficult to get a hold of and a challenge to look at under an electron microscope.”

To overcome that challenge, the UCLA researchers cryogenically froze the tissue samples — which prevented the formation of ice crystals that would have otherwise occluded the synapses had the samples been conventionally frozen. Researchers also did a special biochemical assay for oligomers, and found that the concentration of oligomers in patients who had dementia was much higher than in patients who had the amyloid plaque buildup but no dementia.

Researchers also studied the timing of the biochemical changes in the brain. They found that the accumulation of amyloid beta in the synapses occurred in the earliest stages of the amyloid plaques, and much earlier than the appearance of synaptic p-tau, which did not occur until late-stage Alzheimer’s set in. This result supports the currently accepted “amyloid cascade hypothesis” of Alzheimer’s, which says that the accumulation of amyloid-beta in the brain is one of the first steps in the development of the disease.

The researchers now plan to examine exactly how soluble amyloid-beta oligomers lead to tau pathology and whether therapies that slow the accumulation of amyloid-beta oligomers in the synapses might delay or even prevent the onset of Alzheimer’s-related dementia.

“The study indicates there is a threshold between the oligomer buildup and the development of Alzheimer’s,” Gylys said. “If we can develop effective therapies that target these synaptic amyloid beta oligomers, even a little bit, it might be possible to keep the disease from progressing.”

Gylys said people can reduce their risk for Alzheimer’s through lifestyle and diet choices, but added that one solution is not going to be enough. “Alzheimer’s disease, like heart disease or cancer, is a lot of things going wrong,” she said. “But understanding this threshold effect is very encouraging.”

Other investigators involved in the study were Tina Bilousova, Harry Vinters, Eric Hayden, David Teplow, Gregory Cole and Edmond Teng of UCLA; Carol Miller of the University of Southern California; and Wayne Poon, Maria Corrada, Claudia Kawas, Charles Glabe and Ricardo Albay III of UC Irvine.

The research was supported by grants from the National Institutes of Health and National Institute of Aging.

by Laura Perry, UCLA School of Nursing
 
Author: Guest at 9:30 AM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.