• By Duska Anastasijevic

Why Some With Alzheimer’s Die Without Cognitive Impairment, While Others Do?

July 16, 2014

A Third Protein Provides Clue

Since the time of Dr. Alois Alzheimer himself, two proteins (beta-amyloid (Aβ) and tau) have become tantamount to Alzheimer’s disease (AD). But a Mayo Clinic study challenges the perception that these are the only important proteins accounting for the clinical features of the devastating disease.

In a large clinico-imaging pathological study, Mayo Clinic researchers demonstrated that a third protein (TDP-43) plays a major role in AD pathology. In fact, people whose brain was TDP positive were 10 times more likely to be cognitively impaired at death compared to those who didn’t have the protein, showing that TDP-43 has the potential to overpower what has been termed resilient brain aging. The study was published in the journal Acta Neuropathologica.

Duska Anastasijevic, Mayo Clinic Public Affairs, 507-284-5005, Email: newsbureau@mayo.edu

MULTIMEDIA ALERT: Video and audio are available for download on the Mayo Clinic News Network.

Mayo Clinic researchers studied brains of 342 patients who had died with pathologically confirmed AD and divided them into two groups based on the presence or absence of the protein TDP-43. The protein was found in 195 or 57 percent of the cases.

“We wanted to determine whether the TDP-43 protein has any independent effect on the clinical and neuroimaging features typically ascribed to AD and we found that TDP-43 had a strong effect on cognition, memory loss and medial temporal atrophy in AD,” says Mayo Clinic neurologist Keith Josephs, M.D., the study’s lead investigator and author. “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 patients who suffered from greater cognitive impairment and medial temporal atrophy at the time of death had greater TDP-43 burden and had the protein in a greater number of brain regions.

“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,” says Dr. Josephs.  “Our findings suggest that in order to have AD and be cognitively resilient, TDP-43 must be absent, so it should be considered a potential therapeutic target for the future treatment of AD.

This study was funded by the US National Institute of Heath (NIA) Grants and supported by the Mayo Clinic Alzheimer's Disease Research Center.



Not only should you avoid accepting or declining the meeting from your mobile device, but also avoid deleting the invite message that appears in the Inbox on your device.


"Did you know acting on Outlook meeting invitations from your mobile device (iPhone, Blackberry, etc.) can create potential issues for your calendar? " No, I did not. Thanks for telling us. PS: Why?


Why is a good question. What would it take to fix that?


To Jason, if you have accepted a meeting using Outlook, can you then delete it from your other device?


Working with callers at the Help Desk/Software Support, we’ve discovered that interacting with meeting invitations on a mobile device may cause meetings to disappear or be deleted from a calendar. Acting on meeting invitations from Outlook ensures meetings will be placed on the calendar appropriately. Once a meeting request is opened in Outlook and acted on, it should be automatically moved to the Deleted Items folder (and out of the Inbox on the mobile device). If it is still in the Inbox of the mobile device, best practice is not to interact with it; once the mobile device synchs with the Outlook mailbox it should disappear. – Jenny, HR-Microcomputer Education Services

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