by John Gever for MedPage Today:

When drug giant Eli Lilly announced in August that both EXPEDITION trials of its anti-amyloid drug solanezumab had failed to show a significant benefit, many in the field thought that would be the end of the line for such agents, at least for patients showing clear signs of cognitive impairment.

The failure followed a string of other disappointing results with a variety of agents targeting the rogue protein.

Another monoclonal antibody drug, bapineuzumab, had also shown no clinical benefit in a large trial. Likewise, compounds aimed at inhibiting secretase enzymes responsible for producing beta-amyloid in vivo were disappointing.

And before that, an immunotherapy intended to mobilize the body’s own immune system against beta-amyloid plaques had also failed. Even staunch advocates of the so-called amyloid hypothesis in Alzheimer’s disease — which holds that beta-amyloid protein plaques are a key causative factor in the neurodegeneration that underlies the condition — had changed their thinking.

by Tess Stynes for 4-Traders:

Merck & Co. reached a collaboration, license and supply agreement with General Electric Co.’s health-care business for use of a GE Healthcare investigational imaging agent to support the pharmaceutical company’s lead drug candidate to treat Alzheimer’s disease.

Merck’s investigational Alzheimer’s treatment–called MK-8931–targets a substance in the brain called amyloid. Scientists have hypothesized that the buildup of amyloid in the brain plays a role in Alzheimer’s disease. A number of major pharmaceutical companies have been looking for a treatment to stop the progression of the disease, which impairs memory and cognitive skills in the elderly.

by EurekAlert:

Studies show a naturally occurring protein called beta amyloid may be the key to diagnosis and could even be the answer to treating the neurodegenerative disease.

An arsenal of Alzheimer’s research revealed at the Society of Nuclear Medicine’s 59th Annual Meeting indicates that beta-amyloid plaque in the brain not only is involved in the pathology of Alzheimer’s disease but may also precede even mild cognitive decline. These and other studies advance molecular imaging for the early detection of beta-amyloid, for which one product is now approved in the United States , as a major push forward in the race for better treatments.

“Diagnosis of Alzheimer’s disease can now be made when the patient first presents symptoms and still has largely preserved mental function,” says Christopher Rowe, M.D., a lead investigator for the Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) and professor of nuclear medicine at Austin Hospital in Melbourne, Australia. “Previously there was an average delay of three years between consulting a doctor over memory concerns and the diagnosis of Alzheimer’s, as the diagnosis required the presence of dementia.

by Machines Like Us:

by David Krotz for Berkeley Lab:

For the past five years, volunteers from the City of Berkeley and surrounding areas have come to Lawrence Berkeley National Laboratory to participate in an ongoing study that’s changing what scientists know about Alzheimer’s disease.

The volunteers, most over the age of 70, undergo what can best be described as a brain checkup. They’re asked to solve puzzles and memorize lists of words. Magnetic resonance imaging (MRI) scans image the structure of their brains in exquisite detail. Functional MRI scans allow scientists to watch portions of their brains light up as they form memories. And Positron emission tomography (PET) scans measure any accumulation of beta-amyloid, a destructive protein that’s a hallmark of Alzheimer’s.

The goal of the Berkeley Aging Cohort Study is to reveal how our brains change as we age. The scientists also compare their findings with brain scans of Alzheimer’s patients. They’ve noticed something odd—and perhaps a little hopeful. Some volunteers have the same level of beta-amyloid deposition as an Azheimer’s patient. Yet they show no signs of the disease.

Why is this? How can two people, the same age and with the same signs of the disease, take such different paths?

by Medical XPress:

When brain cells start oozing too much of the amyloid protein that is the hallmark of Alzheimer’s disease, the astrocytes that normally nourish and protect them deliver a suicide package instead, researchers report.

Amyloid is excreted by all neurons, but rates increase with aging and dramatically accelerate in Alzheimer’s. Astrocytes, which deliver blood, oxygen and nutrients to neurons in addition to hauling off some of their garbage, get activated and inflamed by excessive amyloid.

Now researchers have shown another way astrocytes respond is by packaging the lipid ceramide with the protein PAR-4, which independently can do damage but together are a more “deadly duo,” said Dr. Erhard Bieberich, biochemist at the Medical College of Georgia at Georgia Health Sciences University.

“If the neuron makes something toxic and dumps it at your door, what would you do?” said Bieberich, corresponding author of the study published in the Journal of Biological Chemistry. “You would probably do something to defend yourself.”

by Denise Grady for The New York Times

“If there’s something to be done, I want to be in on the ground floor,” said Elizabeth, 67, a woman participating in studies of frontotemporal degeneration at the University of California, San Francisco.

by Salynn Boyles for WebMD

UC Davis researchers have found novel compounds that disrupt the formation of amyloid, the clumps of protein in the brains of people with Alzheimer’s disease believed to be important in causing the disease’s characteristic mental decline. The so-called “spin-labeled fluorene compounds” are an important new target for researchers and physicians focused on diagnosing, treating and studying the disease.

The study, published today in the online journal PLoS ONE, is entitled “The influence of spin-labeled fluorene compounds on the assembly and toxicity of the Aβ peptide.”

“We have found these small molecules to have significant beneficial effects on cultured neurons, from protecting against toxic compounds that form in neurons to reducing inflammatory factors,” said John C. Voss, professor of biochemistry and molecular medicine at the UC Davis School of Medicine and the principal investigator of the study. “As a result, they have great potential as a therapeutic agent to prevent or delay injury in individuals in the earliest stages of Alzheimer’s disease, before significant damage to the brain occurs.”

by UC San Diego Health System

Without p-tau protein present, impact of amyloid is “not significantly different from zero”

According to a new study, the neuron-killing pathology of Alzheimer’s disease (AD), which begins before clinical symptoms appear, requires the presence of both amyloid-beta (a-beta) plaque deposits and elevated levels of an altered protein called p-tau.

Without both, progressive clinical decline associated with AD in cognitively healthy older individuals is “not significantly different from zero,” reports a team of scientists at the University of California, San Diego School of Medicine in the April 23 online issue of theArchives of Neurology.

“I think this is the biggest contribution of our work,” said Rahul S. Desikan, MD, PhD, research fellow and resident radiologist in the UC San Diego Department of Radiology and first author of the study.  “A number of planned clinical trials – and the majority of Alzheimer’s studies – focus predominantly on a-beta. Our results highlight the importance of also looking at p-tau, particularly in trials investigating therapies to remove a-beta. Older, non-demented individuals who have elevated a-beta levels, but normal p-tau levels, may not progress to Alzheimer’s, while older individuals with elevated levels of both will likely develop the disease.”