Alzheimer's Invisible Twin

I just got my University of Washington Brain Wellness Center monthly newsletter, and it had a fascinating article on a newly-identified brain disease.  The article (actually a press release from the National Institute on Aging) was about a "newly-defined Alzheimer's-like brain disorder."  The newly-defined disease is called Limbic-predominant Age-related TDP-43 Encephalopathy, or LATE.  (Say that three times fast.)  It mimics AD and is differentiated from AD at the autopsy.  So far, anyway.  According to the press release, the search is on for biomarkers that would help differentiate it from AD in living patients.

Apparently, LATE advances more slowly than AD, and primarily affects "the oldest of the old."  But in that group it may have a public health impact that exceeds AD.  And if it appears together with AD, dementia may advance more rapidly than with either disease alone. 

TDP-43 is the name of the protein that characterizes the disease.  Its normal role is to help regulate gene expression in the brain and other tissues.  However, it it's misfolded, it can misbehave and cause problems.

What is folding all about?  During the process of building new protein molecules (protein synthesis), chains of amino acids are jostled by water and other molecules (Brownian motion) such that electrical charges along the length of the chain are allowed to attract and repel each other to fold the new protein into a precise shape.  Or so it's hoped.  When things don't go well, you may end up with a misshapen protein that will behave very differently from what's intended.

So LATE is a new research priority.  It will be important to find biomarkers to differentiate it from AD in pools of research test subjects.  If a new drug intervention for AD is tested on a pool where many have LATE and not AD, it will invalidate the results.