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:2/7/2017)... Ind. , Feb. 7, 2017 Zimmer ... leader in musculoskeletal healthcare, will present at the LEERINK ... New York Palace Hotel on Wednesday, February 15, 2017 ... live webcast of the presentation can be accessed at ... replay following the conference via Zimmer Biomet,s Investor Relations ...
(Date:2/3/2017)... , Feb. 3, 2017 A new independent ... Strategy Partners, LLP (IdSP) . Designed to fill a ... complex identity market, founding partners Mark Crego ... combined years just in identity expertise that span federal ... non-profit leadership. The Crego-Kephart combined expertise has a common ...
(Date:2/1/2017)... 1, 2017 IDTechEx Research, a leading provider ... announces the availability of a new report, Sensors for Robotics: ... Continue Reading ... ... robots. Source: IDTechEx Report "Sensors for Robotics: Technologies, Markets and Forecasts ...
Breaking Biology News(10 mins):
(Date:2/27/2017)... , Feb. 27, 2017 AcelRx Pharmaceuticals, ... on the development and commercialization of innovative therapies ... today the U.S. Food and Drug Administration (FDA) ... under section 505(b)(2) for DSUVIA™ (formerly ARX-04) (sufentanil ... patients with moderate-to-severe acute pain in a medically ...
(Date:2/27/2017)... ... ... The Catalyst Midwest premix manufacturing facility has been certified as organic, ... label organic services. , The first organic product is Organic 18 Percent Layer Feed, ... Marketing, which owns the facility. , Catalyst already has received the Safe Feed/Safe ...
(Date:2/24/2017)... ... ... Chef Jodi Abel has returned from her three-week tour through the ... a number of delicious recipes and new techniques to share with her Lajollacooks4u guests. ... province. It is internationally renowned for its incredible wine farms, beautiful environment, boutiques ...
(Date:2/24/2017)... China Cord Blood Corporation (NYSE: CO ) ... blood collection, laboratory testing, hematopoietic stem cell processing and ... results for the third quarter and first nine months ... Third Quarter of Fiscal 2017 Highlights ... increased by 18.6% to RMB200.9 million ($28.9 million). ...
Breaking Biology Technology: