A study at Emory University School of Medicine has marked another step towards developing an effective blood test for Alzheimer’s disease. This study will be published in the August 28 issue of the journal, Neurology. William Hu, MD, PhD and assistant professor of Neurology at the university was the lead author of hits study; collaborators from University of Pennsylvania and Washington University, St. Louis, were also involved.

Six hundred participants from these institutions took part in the study; these participants were either healthy or diagnosed with Alzheimer’s disease (AD) or mild cognitive impairment (MCI). MCI can be a precursor to Alzheimer’s. The scientists measured the levels of 190 proteins in the blood of the participants. Results indicated that 17 proteins were present in significantly different levels in the blood of those with AD or MCI compared to the healthy volunteers. The researchers checked these 17 proteins with data from another 566 people in the multicenter Alzheimer’s Disease Neuroimaging Initiative. From this, they distinguished four proteins (apolipoprotein E, B-type natriuretic peptide, C-reactive protein, pancreatic polypeptide) that correlated with AD and MCI. In an analysis that clustered people into three groups (MCI, high risk of developing AD, and full AD), it was found that changes in blood levels of these foru proteins are linked to levels of beta-amyloid in the cerebrospinal fluid. Beta-amyloid is the protein that is believed to cause Alzheimer’s when accumulated in the brain.
 

While there is a way to go, these biomarkers give hope that a blood test for Alzheimer’s can be possible.

For the publication of the study, please visit http://www.ncbi.nlm.nih.gov/pubmed/22855860.

Source: http://scienceblog.com/56029/blood-test-for-alzheimers-gaining-ground/

Keywords: blood test; Alzheimer’s disease; beta-amyloid

Wendy Liu

August 13, 2012

 
 
Many clinical trials for Alzheimer's Drug failed recently.  Dimebon (Latrepirdine) is one of them.

The drug latrepirdine, known as Dimebon, has been featured in two studies previously published in the journal Molecular Psychiatry.The second study showed that latrepirdine could serve as treatment for Alzheimer’s disease, Parkinson’s, as well as other neurodegenerative conditions.

Led by researchers from Mount Sinai School of Medicine, the drug was tested in three different systems (yeast cells, mice cells, and mammal cells), and each system had an accumulation of alpha-synuclein, a protein that causes neurodegeneration. In all three systems, latrepirdine was able to trigger autophagy, a homeostatic process by which the cells break down their own components. The autophagy decreased the amount of synuclein that built up in the mice’s brains.

In the first study, the researchers found that the drug, by activating autophagy, was able to stop the accumulation of beta-amyloid in the brains of mice with Alzheimer’s disease, and their memories also improved. In addition, it was found that the yeast cells were protected by latrepirdine from the toxicity of alpha-synuclein.

Latrepirdine was approved by Russia in 1983 to be sold as an antihistamine in the country. After being effective in treating animal models with Alzheimer’s disease in the 1990s, it underwent a large Phase II clinical trial in Russia with results showing that it significantly improved cognitive function in Alzheimer’s patients with minimal side effects and was able to maintain that improvement. A Phase III clinical trial was carried out in the United States, but there was so sign of improvement in the Alzheimer’s patients.  Scientists now believe that the trial failed “because of a lack of understanding of how latrepirdine works”.

Currently, the researchers are seeing if the drug can help treat or prevent Parkinson’s disease, Lewy body dementia, etc, all of which are disorders related to high levels of alpha-synuclein.

Sources: http://www.medicalnewstoday.com/articles/248956.php

http://scienceblog.com/56074/drug-reject-may-protect-against-alzheimers-parkinsons-diseases/

Keywords: drug; latrepiridine; alpha-synuclein; Alzheimer’s disease; Parkinson’s disease; research

Wendy Liu

August 14, 2012

 
 
Pro-inflammatory cytokine production can be beneficial to the human body, as it is part of the body’s biological response. However, overproduction of these proteins promotes the development of many deteriorating neurological diseases, such as Alzheimer’s disease (AD) and the neurological damages that are aftereffects of traumatic brain injury (TBI) and stroke. High levels of pro-inflammatory cytokines inhibit proper synaptic communication and function, which eventually leads to damages in the cortex and hippocampus of the brain.

In a study from Northwestern’s Feinberg School of Medicine and University of Kentucky, a new set of drugs have been developed that targets this issue by preventing the overproduction. These drugs target neuroinflammation, a type of brain inflammation that is believed to be a major factor in the injurious nature of diseases ranging from Alzheimer’s to Parkinson’s, as well as brain injuries. The drugs, currently represented by MW151 and MW189, have been tested in previous animal studies. MWI151 was given to a six-month old (the time at which the level of pro-inflammatory cytokines being to increase) mice that are genetically engineered to develop AD for three times a week; then, their brains were examined at eleven months of age, the time at which the conditions of AD are visible. The development of the full-blown AD was avoided as the level of cytokines had returned to normal levels and their synapses were working properly. Mice that were not given the drug still had high levels of pro-inflammatory cytokines and had synaptic malfunction.  In another cases, it has also helped decrease the nerve damage caused by TBI by preventing overproduction of pro-inflammatory cytokines and blocking the activation of glia cells. Success was also met when the drug was tested in mice to prevent the development of multiple sclerosis.

Phase one of the first human clinical trial has been completed, but these current studies have shown that the therapy time window is limited, so for future clinical trials, further studies involving models of other diseases and time windows will be conducted. With this new development, the future of early therapy to prevent the development of neurological diseases and the long-term complications of TBI and strokes seems promising.

Keywords: inflammation; pro-inflammatory cytokines; drug; Alzheimer’s disease; traumatic brain injury

Sources: http://www.northwestern.edu/newscenter/stories/2012/07/brain-inflamation-drug.html                   

             

               http://www.jneurosci.org/content/32/30.abstract.pdf (Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model That Exhibits Age-Dependent Progression of Alzheimer’s Disease-Related Pathology)

Wendy Liu

July 25, 2012