Third Protein May be Catalyst for Alzheimer's Disease

  • The masses of plaques and tangles found during autopsies of older human brains are thought to be caused by a combination of beta-amyloid and tau proteins. These plaques and tangles have long been considered by many scientists to be the cause of Alzheimer’s disease. A looming question, however, is that the same type of plaques and tangles are also frequently found in the autopsied brains of people without Alzheimer’s disease symptoms. The Mayo Clinic has been conducting research hoping to finding out why this is the case. Now, it looks as though they may have found the answer.

     

    According to an article in the March journal Acta Neuropathologica, the Mayo Clinic researchers demonstrated in a large clinico-imaging pathological study that a third protein called TDP-43 plays a major role in Alzheimer’s disease. The study concluded that people whose brain was TDP positive were 10 times more likely to be cognitively impaired at death than those who didn't have the protein. The Mayo scientists say that their finding proves that TDP-43 has the potential to overpower what has been termed resilient brain aging. Resiliency is required for the body to fight off negative changes in the body.

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    For this study, Mayo Clinic researchers examined the brains of 342 patients who had died with pathologically confirmed Alzheimer’s disease. The brains were divided into two groups based on the presence or absence of the protein TDP-43. Researchers found the protein in 195 subjects which converts to 57 percent of the cases.

     

    Mayo Clinic neurologist Keith Josephs, M.D., the study's lead investigator and author, was quoted as saying, "We wanted to determine whether the TDP-43 protein has any independent effect on the clinical and neuroimaging features typically ascribed to AD... we found that TDP-43 had a strong effect on cognition, memory loss and medial temporal atrophy in AD. In the early stages of the disease when AD pathology was less severe, the presence of TDP-43 was strongly associated with cognitive impairment. Consequently, TDP-43 appears to play an important role in the cognitive and neuroimaging characteristics that have been linked to AD."

     

    The study also found that people who suffered the most extreme cognitive impairment and brain atrophy at the time of death had a greater amount of TDP-43 affecting more regions of the brain than those with lower amounts of the protein.

     

    "This is why we believe that TDP-43 pathology could help shed light on the phenomenon of resilient cognition in AD and explain why some patients remain clinically normal, while others do not, despite both having similar degrees of AD pathology,” Dr. Josephs explained.

     

    The study suggests that in order to have Alzheimer’s disease and yet be cognitively resilient, the protein TDP-43 must not be present. The researchers feel that TDP-43 should be considered a potential therapeutic target for the future treatment of Alzheimer's disease.

     

    While this recent Mayo Clinic study doesn’t negate the current thinking that plaques and tangles are responsible for Alzheimer’s disease, it does seem to point to a need to shift the focus from beta-amyloid and tau to whether or not a third protein – TDP-43 – is present. This could mean starting from scratch for some pharmaceutical researchers.

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    As with most studies, more information will need to be gathered before pharmaceutical companies devote huge resources to develop a drug that targets yet another protein. We can hope that the correct direction for Alzheimer’s research will soon be agreed upon by most researchers so that cooperative efforts can enhance the global fight to end the Alzheimer's epidemic. 

     

    For more information about Carol visit  www.mindingourelders.com or www.mindingoureldersblogs.com.

       

    Sources:

              

    Medical News Today (2014, April 25) Why do some people with Alzheimer's disease die without cognitive impairment, while others do? Retrieved from http://www.medicalnewstoday.com/releases/275930.php?utm_content=buffer5c000&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer


    Acta Neuropathologica, 'TDP-43 is a key player in the clinical features associated with Alzheimer’s disease', Keith A. Josephs, Jennifer L. Whitwell, Stephen D. Weigand, et al, March 2014.

     

Published On: May 20, 2014