Scientists at Cambridge’s Department of Chemistry have been able to construct a detailed map that shows how the formation of proteins in the brain can lead to a build-up so massive that it can lead to the development of numerous brain-damaging diseases, chief among them is Alzheimer’s. In 2010, the Alzheimer’s Research Trust found that with dementia alone, it cost the UK economy E23 billion, way more than cancer and heart disease combined cost.
    Normally, proteins are made up of chemical building blocks known as amino acids, which are joined together in a code ordered by our DNA. New proteins appear as long, thin strips, which are then intricately folded to properly carry out their designated biological function. However, there are points at which the protein can ‘misfold,’ or unfold and get tangled together with other newly-made proteins. The tangles stick to one another until they number in the millions, known as amyloid fibrils, and they start the huge deposits of proteins known as plaque, which are so huge that they are insoluble.  
    When the level of plaque in the brain reaches a critical level, a chain reaction is set off, and new focal points of tendrils form. From these tendrils, a smaller number of proteins, known as toxic oligomers, can easily diffuse through membranes, effectively killing neurons, causing memory loss, and other dementia symptoms.
    This new groundbreaking information required scientists to come together, using kinetic experiments with a framework of theory. Master equations, more commonly used in the fields of chemistry and physics, aided researchers in their efforts to better understand a disease such as Alzheimer’s, and how better to fight it.

By Lauren Horne

    University of Cambridge (2013, May 20). Molecular trigger for Alzheimer's disease identified. ScienceDaily. Retrieved May 22, 2013,
    Samuel I. A. Cohen, Sara Linse, Leila M. Luheshi, Erik Hellstrand, Duncan A. White, Luke Rajah, Daniel E. Otzen, Michele Vendruscolo, Christopher M. Dobson, and Tuomas P. J. Knowles. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218402110
A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine.  Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact,  preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.

Dr. Michael Mullan M.D., Ph.D
President & CEO
Roskamp Institute
_  Studies on Brain imaging suggest that Alzheimer’s and other forms of most prevalent dementia’s may spread within nerve networks in the brain by moving directly between connected neurons, in a way  by propagating in all directions. Studies concluded that a nerve region's connectedness to a disease hot spot trumps overall connectedness, spatial proximity and loss of growth-factor support in predicting its vulnerability to the spread of Alzheimer’s.

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A new technology, recently approved by the FDA, allows researchers to detect amyloid plaques that often suggest Alzheimer's disease.  Created by Eli Lilly, Amyvid is a drug that, when used before a PET scan, will highlight amyloid plaque in the brain.  This method is much more preferable for diagnosis than the current method of performing an autopsy. 


            A new study shows that reducing the iron levels in blood plasma may help protect the brain          from changes. There is previous evidence that there are changes in the way the  human body      handles iron and other metals (zinc, cooper) before it shows Alzheimer's symptoms. In the             study, rats are fed a high cholesterol diet which causes them to build up plaques of a protein   called beta-amyloid and develop changes in the tau proteins. The study deals with a new drug        called deferiprone which lowered the iron concentration in the blood plasma of the rabbit and the level of beta-amyloid and the tau proteins in the brain. 


              At the University of South Florida (USF) researchers have discovered that the amyloid     precursor protein (APP) which is associated with Alzheimer's Disease regulates its own growth.        This discovery has the potential to allow scientists to treat and possible prevent the disease by controlling the regulation of the protein.  Through their research at USF, it has been determined         that the growth of APP is dependent on an enzyme (BACE1) excreted by the amyloid leading to       the theory that, if the reaction between the BACE1 and APP was blocked, Alzheimer's disease             may see its end. 


              Researchers have shown that elevated pulse pressures in older humans with Alzheimer's disease    are at a higher risk to get Cerebrovascular disease. Recent studies have shown that patients with   Alzheimer's disease that have a high pulse pressure may impair the clearance of beta-amyloid            from the brain. Other studies show that high pulse pressures increases the chance of   Cerebrovascular disease which contributes to the cause of Alzheimer's disease.

           A groundbreaking new test for the early detection of Alzheimer's disease is being developed at a research facility just north of Sydney, Australia.  Currently, the only prevalent tests of such             nature are invasive and expensive.  However, the test being developed in Syndey is a cheap            blood test that checks for a change in levels of a specific protein marker over a year in order to      determine if a patient is in deed affected by the lethal disease.  The earlier Alzheimer's is      detected, the more likely it can be slowed and even stopped.

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