A red dye derived from lichens that has been used for centuries to color fabrics and food appears to reduce the abundance of small toxic protein aggregates in Alzheimer’s disease. The dye, a compound called orcein, and a related substance, called O4, bind preferentially to small amyloid aggregates that are considered to be toxic and cause neuronal dysfunction and memory impairment in Alzheimer’s disease. O4 binding to small aggregates promotes their conversion into large, mature plaques which researchers assume to be largely non-toxic for neuronal cells. Read the full story in NATURE CHEMICAL BIOLOGY.
For decades the amyloid hypothesis has dominated the research field in Alzheimer’s disease. The theory describes how an increase in secreted beta-amyloid peptides leads to the formation of plaques, toxic clusters of damaged proteins between cells, which eventually result in neurodegeneration. Scientists at Lund University, Sweden, have now presented a study that turns this premise on its head. The research group’s data offers an opposite hypothesis, suggesting that it is in fact the neurons’ inability to secrete beta-amyloid that is at the heart of pathogenesis in Alzheimer’s disease. Read the report of their work in Journal of Neuroscience.
A tiny piece of a critical receptor that fuels the brain and without which sentient beings cannot live has been discovered by University at Buffalo scientists as a promising new drug target for Alzheimer’s and other neurodegenerative diseases.
The research on the NMDA (N-methyl-D-aspartate) receptor was being published online in Nature Communications.
Intranasal insulin therapy may have beneficial effects on cognition and function among patients with Alzheimer’s disease, a pilot study suggested.
Patients who received 20 IU of intranasal insulin daily for four months had improvements on delayed story recall tests (P=0.02, Cohen f effect size=0.36), according to Suzanne Craft, PhD, of the Veterans Affairs Puget Sound Health Care System in Seattle, and colleagues.
And compared with placebo, baseline scores on the Dementia Severity Rating Scale were maintained over the study period in patients receiving either 20 IU or 40 IU of the insulin (P=0.01 for both, Cohen f = 0.38 for 20 IU and 0.41 for 40 IU), the researchers reported online in the Archives of Neurology.
A pair of papers published in Nature Genetics reports on new genes associated with Alzheimer’s disease, bringing the total number of genes associated with the disease to 10, The New York Times says. One group of researchers studied Europeans with Alzheimer’s and the other studied Americans, and both groups homed in on similar genes. The newly unearthed genes increase a person’s risk of developing the disease by about 10 percent to 15 percent — a more modest effect than that of APOE, which can raises a person’s risk by 400 percent to 1,000 percent depending on the number of copies of the gene the person has. Read the European study. Read the American study.
Results from a new study contribute to growing evidence that if one of your parents has Alzheimer’s disease, the chances of inheriting it from your mother are higher than from your father. The study is published in the March 1, 2011, print issue of Neurology. The researchers found that people with a mother who had Alzheimer’s disease had twice as much gray matter shrinkage as the groups who had a father or no parent with Alzheimer’s disease. In addition, those who had a mother with Alzheimer’s disease had about one and a half times more whole brain shrinkage per year compared to those who had a father with the disease. Request article from Markus Library.
Scientists have isolated a set of proteins that accounts for over 130 brain diseases, including diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsies and forms of autism and learning disability. The team showed that the protein machinery has changed relatively little during evolution, suggesting that the behaviors governed by and the diseases associated with these proteins have not changed significantly over many millions of years. The findings open several new paths toward tackling these diseases. In the brain synapses have a set of proteins, which, like the components of an engine, bind together to build a molecular machine called the postsynaptic density — also known as the PSD.
A team of scientists, led by Professor Seth Grant at the Wellcome Trust Sanger Institute and Edinburgh University, have extracted the PSDs from synapses of patients undergoing brain surgery and discovered 1461 proteins, each one encoded by a different gene. This has made it possible, for the first time, to systematically identify the diseases that affect human synapses and provides a new way to study the evolution of the brain and behaviour. Read more in the Dec 19 issue of Nature Neuroscience.
Attempts to find a lone biomarker for Alzheimer’s disease — whether it’s in blood, spinal fluid, or the brain — have largely failed. The Texas Alzheimer’s Research Consortium project conducted a longitudinal case-control study, using stored blood samples to develop an algorithm that separates patients with Alzheimer’s disease from controls. The biomarker assays looked at hundreds of proteins, including thrombopoietin, TNF-alpha, creatine kinase, and various interleukins. The his team focused on a large array of blood-based proteins, since assay technology has now made it possible to evaluate large amounts of data. Screening for these biomarkers and factoring in age, sex, education, and APOE status led to a sensitivity of 0.94 and a specificity of 0.84, as reported by Sid O’Bryant, PhD, of Texas Tech University, in Lubbock, Texas, and colleagues in the Archives of Neurology. They also saw that many of the proteins with the highest importance were inflammatory in nature, which suggests that the existence of an inflammatory-related endophenotype of Alzheimer’s disease “may provide targeted therapeutic opportunities for this subset of patients.”
Monday Lecture Series
The Role of SIRT1 in Neurodegenerative Diseases
Gizem Donmez, Ph.D.,
Post Doctoral Fellow
Glenn Laboratory for the Science of Aging, Department of Biology
Massachusetts Institute of Technology
September 27, 2010
4:00 p.m. Welch Hall Level Two
Recommended Review Article:
Haigis MC, Sinclair DA. 2010. Mammalian Sirtuins: Biological Insights and Disease Relevance.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 5: 253-295
Donmez G, Wang D, Cohen DE, et al. 2010. SIRT1 Suppresses beta-Amyloid Production by Activating the alpha-Secretase Gene ADAM10. CELL 142 ( 2):320-332
Albani D, Polito L, Forloni G. 2010. Sirtuins as Novel Targets for Alzheimer’s Disease and Other Neurodegenerative Disorders: Experimental and Genetic Evidence. JOURNAL OF ALZHEIMERS DISEASE 19(1): 11-26 PLEASE CONTACT MARKUS LIBRARY FOR A COPY OF THIS ARTICLE.
Gao J, Wang WY, Mao YW, et al. 2010. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. NATURE 466( 7310): 1105-U120
Michan S, Li Y, Chou MMH, et al. 2010. SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity. JOURNAL OF NEUROSCIENCE 30(29): 9695-9707
Tang BL, Chua CEL. 2010. Is systemic activation of Sirt1 beneficial for ageing-associated metabolic disorders? BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 391(1): 6-10
Tang BL. 2009. Sirt1′s Complex Roles in Neuroprotection. CELLULAR AND MOLECULAR NEUROBIOLOGY 29(8):1093-1103
ScienceDaily (Aug. 2, 2010) — A team of scientists at the University of California, Davis and the University of Auckland has discovered that neuroglobin may protect against Alzheimer’s disease by preventing brain neurons from dying in response to natural stress. Neuroglobin protects cells from stroke damage, amyloid toxicity and injury due to lack of oxygen. Neuroglobin occurs in various regions of the brain and at particularly high levels in neurons. Recent studies have hinted that neuroglobin protects cells by maintaining the function of mitochondria and regulating the concentration of important chemicals in the cell. However, the exact mechanisms by which neuroglobin protects cells from dying a natural death has, until now, remained unclear. Click here for more on the research that resulted in these insights.