Navigation Links
Pinpointing a culprit molecule in Alzheimer's disease

One puzzle in Alzheimer's disease (AD) research is why mice engineered to have the abnormal protein underlying the disease in humans show little pathology of the disease. Specifically, such mice are genetically altered to overproduce mutant human amyloid precursor protein (APP). It is this protein that, when clipped by enzymes, produces the amyloid beta (Ab) peptide that clusters into the amyloid plaque that clogs the brain and kills brain cells.

The clipping of APP produces two types of amyloid beta peptide--one 40 amino acid units long (Ab40) and one 42 units long (Ab42). Circumstantial evidence has suggested that Ab42 is the "stickier" of the two forms, and underlies the pathology of the disease.

Now, researchers led by Eileen McGowan and Todd Golde of the Mayo Clinic College of Medicine report in the July 21, 2005, issue of Neuron definitive proof that Ab42 is, indeed, the culprit molecule. In their experiments, they created transgenic mice that overproduced either Ab40 or Ab42 in the absence of overproduction of APP. Thus, they could precisely study the role of each of these molecules in AD pathology.

Their studies of the mice revealed that the Ab40 mice showed little amyloid disease pathology in the animals' brains, while the Ab42 mice showed extensive accumulation of amyloid plaque and resulting neural damage. What's more, when the researchers crossed the Ab42 mice with those producing mutant APP, they saw a massive increase in amyloid deposition that was more than the additive effect of the two mutations.

The researchers pointed out that test tube studies have shown that Ab42 aggregates more readily. "Thus, the simplest explanation for the complete lack of pathology in the [Ab40] mice would be the relative inability of Ab40 to initiate nucleation events capable of promoting amyloid deposition," they wrote.

One question the new transgenic mice might help address, wrote the researchers, is whether Ab peptide does damage i nside brain cells or outside--"intracellularly." Transgenic mice produced by other researchers have not settled this question, because the peptide was not efficiently secreted by the cells in those mice. However, wrote McGowan and colleagues, "The [Ab] mice that we have developed are clearly distinct from these other "minigene" models in that they efficiently secrete Ab. To date we have little evidence for the accumulation of intracellular Ab in these mice; thus, they provide an excellent tool to study the effects of secreted Ab independently of APP transgenes."

McGowan et al.: "Aß42 is Essential for Parenchymal and Vascular Amyloid Deposition in Mice" Publishing in Neuron, Vol. 47, July 21, 2005, pages 191?99. DOI 10.1016/j.neuron.2005.06.030. www.neuron.org


'"/>

Source:Cell Press


Related biology news :

1. Pinpointing the cause of a neurodegenerative disorder
2. Chemists create Superbowl molecule; May lead to better health
3. Key molecule in plant photo-protection identified
4. Inflammatory molecules released by pollen trigger allergies
5. Researchers discover molecule that causes secondary stroke
6. Yale researchers identify molecule for detecting parasitic infection in humans
7. Scientists identify molecule that regulates well-known tumor suppressor
8. Medical molecules designed to respond to visible light that can penetrate tissue
9. Researchers find promising cancer-fighting power of synthetic cell-signaling molecule
10. Chemists synthesize molecule that helps body battle cancers, malaria
11. DNA constraints control structure of attached macromolecules
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/23/2017)... ITHACA, N.Y. , June 23, 2017  IBM ... in dairy research, today announced a new collaboration using ... the chances that the global milk supply is impacted ... project, Cornell University has become the newest academic institution ... Chain, a food safety initiative that includes IBM Research, ...
(Date:5/6/2017)... , May 5, 2017 ... just announced a new breakthrough in biometric authentication ... exploits quantum mechanical properties to perform biometric authentication. These ... smart semiconductor material created by Ram Group and ... finance, entertainment, transportation, supply chains and security. Ram ...
(Date:4/13/2017)... April 13, 2017 UBM,s Advanced Design and ... will feature emerging and evolving technology through its 3D ... will run alongside the expo portion of the event ... and demonstrations focused on trending topics within 3D printing ... and manufacturing event will take place June 13-15, 2017 at ...
Breaking Biology News(10 mins):
(Date:10/7/2017)... ... October 06, 2017 , ... ... providing advanced instruments and applications consulting for microscopy and surface analysis, Nanoscience ... application consulting, Nanoscience Analytical offers a broad range of contract analysis services ...
(Date:10/7/2017)...  The 2017 Nobel Prize in Chemistry recognizes ... Joachim Frank and Richard Henderson ... (cryo-EM) have helped to broaden the use ... The winners worked with systems manufactured by Thermo ... resolved, three-dimensional images of protein structures that lead ...
(Date:10/6/2017)... Washington, D.C. (PRWEB) , ... October 06, 2017 ... ... Cure) will host a lunch discussion and webinar on INSIGhT, the first-ever adaptive ... INSIGhT Principal Investigator, Dana-Farber Cancer Institute. The event is free and open to ...
(Date:10/5/2017)... ... 2017 , ... Understanding the microbiome, the millions of bacteria that live in ... Are My Future, the newest exhibit on display at the University City Science Center’s ... through the lens of the gut microbiome. , Gut Love opens October 12, ...
Breaking Biology Technology: