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.”

by News Medical

In Alzheimer’s disease, brain neurons become clogged with tangled proteins. Scientists suspect these tangles arise partly due to malfunctions in a little-known regulatory system within cells. Now, researchers have dramatically increased what they know about this particular regulatory system in mice. Such information will help scientists better understand Alzheimer’s and other diseases in humans and could eventually provide new targets for therapies.

In a study released online in the Proceedings of the National Academy of Sciences Early Edition this week, the team at least doubled the number of proteins found to be subject to a type of regulation based on a sugar known as O-GlcNAc (oh-GLIK-nak). The O-GlcNAc system likely adds another layer of control to the proteins that serve as a brain cell’s widgets and gears — control that might be muddled in Alzheimer’s brains known to have problems in sugar metabolism.

by Harvard Gazette

Under normal circumstances, the tau protein is a hard-working participant in memory and brain functioning.  But in Alzheimer’s disease and other neurodegenerative diseases, tau not only ceases to play a productive role in brain health, but actually undergoes a Jekyll-and-Hyde transformation to become a misshapen villain that destroys brain cells.

Now a novel antibody technology developed by a team at Harvard-affiliated Beth Israel Deaconess Medical Center (BIDMC) provides the first clear distinction between two tau isoforms — one healthy and one disease-causing — and demonstrates that only the disease-causing isoform is found in the neurons of Alzheimer’s patients and is exhibited at a very early stage of disease.

Described in the March 30 issue of the journal Cell, the findings raise the intriguing possibility that the development of antibodies and vaccines that target only the disease-causing tau isoform could be used to diagnose, treat, and potentially even prevent Alzheimer’s.

by The Hindu

Scientists claim to have moved a step closer to developing a vaccine against Alzheimer’s, after they discovered a way to identify which proteins in the brain mutate and cause memory loss.

A team at Beth Israel Deaconess Medical Centre in Boston claims the vaccine could be used to treat Alzheimer’s disease or even prevent the most common form of dementia from taking hold in the first place by giving it to patients in the early stages of the illness.

In fact, the scientists claim to have already developed new antibodies to both diagnose and treat Alzheimer’s, the ’Daily Express’ reported.

These target Alzheimer’s-causing protein of a type known as tau and raise the possibility of an immunisation jab given at an early stage of the disease. Normally, tau protein is a hard-working participant in memory and brain functioning.

But in Alzheimer’s and other neuro-degenerative diseases, it not only stops playing a productive role in brain health, it becomes a misshapen attacker that destroys brain cells.

by Medical Xpress

Under normal circumstances, the tau protein is a hard-working participant in memory and normal brain functioning.

But as is becoming increasingly evident, in Alzheimer’s disease and other neurodegenerative diseases, tau not only ceases to play a productive role in brain health, but actually undergoes a Jekyll-and-Hyde transformation to become a misshapen villain that destroys brain cells.

Now a novel antibody technology developed by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) provides the first clear distinction between two tau isoforms – one healthy and one disease-causing – and demonstrates that only the disease-causing isoform is found in the neurons of Alzheimer’s patients and is exhibited at a very early stage of disease.

Described in the March 30, 2012 issue of the journal Cell, the findings raise the intriguing possibility that the development of antibodies and vaccines that target only the disease-causing tau isoform could be used to diagnose, treat and potentially even prevent Alzheimer’s before the onset of debilitating symptoms.

by Medical XPress

Repeated stress triggers the production and accumulation of insoluble tau protein aggregates inside the brain cells of mice, say researchers at the University of California, San Diego School of Medicine in a new study published in the March 26 Online Early Edition of the Proceedings of the National Academy of Sciences.

The aggregates are similar to neurofibrillary tangles or NFTs, modified protein structures that are one of the physiological hallmarks of Alzheimer’s disease. Lead author Robert A. Rissman, PhD, assistant professor of neurosciences, said the findings may at least partly explain why clinical studies have found a strong link between people prone to stress and development of sporadic Alzheimer’s disease (AD), which accounts for up to 95 percent of all AD cases in humans.

“In the mouse models, we found that repeated episodes of emotional stress, which has been demonstrated to be comparable to what humans might experience in ordinary life, resulted in the phosphorylation and altered solubility of tau proteins in neurons,” Rissman said. “These events are critical in the development of NFT pathology in Alzheimer’s disease.”

by Kristin Shine for Dementia Today

New research in humans published today reveals that the so-called FKBP52 protein may prevent the Tau protein from turning pathogenic. This may prove significant for the development of new Alzheimer’s drugs and for detecting the disease before the onset of clinical symptoms.

A study published online today in the Journal of Alzheimer’s Disease, for the first time demonstrates that the FKBP52 protein, discovered by Prof. Etienne BAULIEU twenty years ago, may prevent hyperphosphorylation of Tau protein, which has been shown to characterise a number of cerebral neurodegenerative diseases, including Alzheimer’s Disease (AD).

This work has been carried out by Professor Etienne Baulieu and his research team at Inserm (National Institute for medical research in France) with the support of philanthropists who help the Institut Baulieu, based in France.

Limited research exists on Tau and its role in the development of AD, but it is known that many neurodegenerative diseases are characterised by the deposition of pathological hyperphosphorylated forms of Tau protein, into structures known as ‘Tau tangles’. The mechanism of Tau toxicity is unclear and there are currently no drug treatments targeting Tau, nor any biomarkers that predict the risk of a future “Tauopathy”. Professor Baulieu decided to focus on Tau abnormalities and was the first to discover in 2010, an interaction between Tau, and the FKBP52 protein.

by Crystal Phend for Medpage Today

Antioxidant supplements don’t appear to have an impact on cerebrospinal fluid (CSF) biomarkers related to Alzheimer’s disease, a clinical trial determined.

The combination of vitamin E, vitamin C, and alpha-lipoic acid did not lower levels of the amyloid and tau proteins that make up the plaques and tangles seen in the brain with Alzheimer’s disease, Douglas R. Galasko, MD, of the University of California San Diego, and colleagues found.

The combination did reduce CSF levels of the oxidative stress biomarker F2-isoprostane by 19% but raised a safety concern with faster decline in cognitive scores, they reported online in the Archives of Neurology.

The popular antioxidant coenzyme Q (CoQ) had no significant impact on any CSF measures in the Alzheimer’s Disease Cooperative Study antioxidant biomarker trial. Oxidative damage is widespread in the brain in Alzheimer’s disease and contributes to neuronal damage, Galasko’s group explained.

Some prior observational evidence has pointed to lower Alzheimer’s risk with an antioxidant-rich diet, although prevention trials with supplements have had mixed results, they noted.

by Washington University in St. Louis

A new marker of Alzheimer’s disease can predict how rapidly a patient’s memory and other mental abilities will decline after the disorder is diagnosed, researchers at Washington University School of Medicine in St. Louis have found.

In 60 patients with early Alzheimer’s disease, higher levels of the marker, visinin-like protein 1 (VILIP-1), in the spinal fluid were linked to a more rapid mental decline in the years that followed.

Scientists need to confirm the results in larger studies, but the new data suggest that VILIP-1 potentially may be a better predictor of Alzheimer’s progression than other markers.

“VILIP-1 appears to be a strong indicator of ongoing injury to brain cells as a result of Alzheimer’s disease,” says lead author Rawan Tarawneh, MD, now an assistant professor of neurology at the University of Jordan. “That could be very useful in predicting the course of the disease and in evaluating new treatments in clinical trials.”

by Mark Hollmer for Fierce Biotech Research

Even as researchers become increasingly concerned about finding a drug that can manage or defeat Alzheimer’s disease, scientists at Canada’s Simon Fraser University bet the answer comes down to sugar.

Rather than reaching for high-sugar foods to protect your brain, however, their discovery here is more elemental.

Keep sugar levels stable in the brain protein tau, the scientists believe, and the action could slow Alzheimer’s progression, or even prevent the disease from happening. What’s more, they’ve come up with a chemical inhibitor that might prevent depletion of those vital sugar molecules.