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Researchers at Lund University in Sweden headed by Professor Singerup Linse and Erik Helistrand have recently identified a molecular mechanism behind the crucial step in Alzheimer’s that leads to the death of brain cells.
The neurological disease is associated, as a general statement, with memory loss and changes in personality.  The research at Lund helps identify on a molecular level the chemical reactions which cause plaque, a major benchmark in the progression of the disease, to form.   Amyloid beta in its soluble form, found naturally within the brain, acts as a building block and turns into plaque called amyloid fibrils, though the exact pathways of these reactions remain unclear.  An early section of the process of formation of fibrils is two small protein fragments of amyloid beta coming together within a nucleus of a cell to form a fibril.  Lund University’s study suggests that fibrils have a catalytic surface, allowing reactions to happen quicker while touching them, creating new nuclei which in turn aid the proliferation of more fibrils, causing exponential growth in plaque formation.  After a small but crucial amount of amyloid fibrils are created, more immediately surface to begin a self-perpetuating process key to understanding Alzheimer’s.  These findings dash what was previously believed; that fibrils formed in single nuclei reactions as a uniform process.  More profound perhaps than the catalytic surface is the discovery that this aggregation of amyloid fibrils creates toxic oligomers, small groups of proteins.  These oligomers have been identified as neurotoxins that play a significant part in cell-death.
It is the hope of Professor Linse that new medicines targeted at shutting down the catalyzation of amyloid fibrils and the resultant neurotoxins can slow or even stop the progression of the disease. For now, it is heartening that ongoing Alzheimer’s research is yielding new information about the degenerative disease and possible ways to fight its progression.

References:
1)  S. I. A. Cohen, S. Linse, L. M. Luheshi, E. Hellstrand, D. A. White, L. Rajah, D. E.  Otzen, M. Vendruscolo, C. M. Dobson, T. P. J. Knowles. Proliferation of amyloid- 42 aggregates occurs through a secondary nucleation mechanism. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218402110
2) Lund University (2013, May 29). Molecular chain reaction in Alzheimer’s disease. ScienceDaily. Retrieved May 30, 2013, from http://www.sciencedaily.com /releases/2013/05/

Keywords: Alzheimer’s disease, Amyloid Beta Protein

Article By: Lauren Horne (edited by Emma Henson)

Roskamp Institute is devoted to find cure for brain related disorders. Its a non-profit research institute located at Sarasota, Florida. Dr. Michael Mullan is the head and CEO of the Roskamp Institute.


 
 
Alzheimer’s disease (AD) characterized by two main features in the brain, an extracellular accumulation of beta-amyloid peptide (Aβ) into plaques and an intracellular buildup of neurofibrillary tangles made of a protein called tau. In addition, it has also been found that the brains of AD patients are continuously present in inflammatory states.

The neurofibrillary tangles are results of an accumulation in neuronal cells of tau protein that has been hyper-phosphorylated and self-assembled into a new form. The buildup of Aβ is a likely cause for the formation of the neurofibrillary tangles in Alzheimer’s patients.

Inflammation in the brain also has a possible link to the accumulation of Aβ. The Roskamp Institute has found that the binding of CD40 ligand (CD40L) to its receptor CD40 is harmful for AD. This proved to be true in a transgenic mouse model for AD TG2576, as prohibiting the binding of CD40-CD40L lessened Aβ buildup and the neuroinflammation.

In a study published in Brian Research, the Roskamp Institute reported findings that indicated that a decrease in the hyper-phosphorylation of the tau protein is not related to the accumulation of Aβ. A CD40 or CD40L deficiency in the mouse model for AD Tg2576 also decreased the hyper-phosphorylation of the tau protein, which implies that the CD40-CD40L pathway has a direct impact on tau phosphorylation.

These studies and findings indicate that the CD40-CD40L pathway has a direct effect on the two main characteristics of AD, which increases the possibility for it to be targeted in future therapeutic solutions.

 

For more information and updates on Alzheimer’s disease, please visit

http://www.rfdn.org
http://www.roskampinstitute.us
http://www.michaelmullan.us
http://www.michaelmullangroup.com

Wendy Liu

August 3, 2012