Researchers have published a paper in Neurology looking at how the APOE4 gene might play a role in Alzheimer’s Disease. The researchers looked at a Murine model and found evidence that the enzyme Cyclophilin A may be playing a role in the development of Alzheimer’s Disease mediated through APOE4. They found that in APOE4 carriers there was a five-fold increase in the levels of Cyclophilin A in the Pericytes, there was a reduction of blood flow in the brain and an increase in the passage into the brain of substances including Thrombin. The Pericytes are cells that form an integral part of the Blood-Brain Barrier. They found that when Cyclophilin A was blocked in APOE4 carriers there was a reduction in the passage of a number of the previously identified substances in the brain as well as an improvement in blood flow. The researchers have thus formulated an interesting and testable hypothesis about the pathogenesis of Alzheimer’s Disease in relation to one gene variant – APOE4.
Cyclophilin A in a complex with Cyclosporin (shown in yellow), Fvasconcellos, Public Domain
From 2014, the National Institute of Clinical Excellence (NICE) will no longer decide whether drugs can or cannot be prescribed. This responsibility will pass to the Department of Health although NICE will continue to evaluate the cost-effectiveness of drugs.
Researchers publishing results from the Rush Memory and Aging Study in the Archives of General Psychiatry have found further evidence that having a strong sense of purpose in life can slow down the progression of Alzheimer’s Disease (paper available here). There were 246 people with Alzheimer’s Disease who had passed away at the time of the study (there were 1400 subjects in the Rush Memory and Aging study at baseline). Global cognition was assessed using 21 tests of cognition and a Z-statistic was used to represent the outcomes. The researchers used a model which incorporated pathological changes at post-mortem as well as global cognitive scores and other variables. They compared subjects with the 90th percentile of scores on Ryff’s Scale of Psychological Well-Being (one of two main rating scales for purpose in life) and those with the 10th percentile score and graphed these (see Fig 1 in the paper). The researchers identified a significant contribution of well-being scores to the global cognitive scores. A higher score of purpose in life was significantly associated with a higher score on global cognition in the model. Curiously though there was no corresponding relationship of well-being scores to neuropathology findings.
A trial is underway involving an antibody to Amyloid, which according to the Amyloid Cascade Hypothesis plays a central role in Alzheimer’s Disease (APOE4 discussed above is also related to Amyloid). The study is a preventative trial to reduce the future prevalence of Alzheimer’s Disease in a cohort who have not yet developed the disease.
There is a brief discussion of the future of drug development in this article which includes a look at some of the barriers as well as current trends.
Professor Alistair Burns talks to Professor Rosser about Dementia research in this video
There is an interesting piece on Thomas Kuhn’s ‘The Structure of Scientific Revolutions’ here.
Researchers have announced the discovery of the world’s oldest flutes (estimated at 42000 years before present) in the Geissenkloesterle Cave in Germany. Excavations in caves in this region have produced a number of interesting findings and are attributed to the Aurignacian culture. However the controversial Divje Babe flute in Slovenia is dated to 43100 years before present and would predate the above flute although the validity of this specimen has been disputed.
A 3D reconstruction of Ichthyostega suggests that it would not have been able to walk on land. Icthyostega is an example of a Tetrapod (having four legs). Tetrapods
are were thought to have been the first animals to walk on land (an important evolutionary event) and are a distant human ancestor.
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