Abnormal Proteins and Genetics in Frontotemporal Dementia

Yesterday’s New York Times had a good article on three proteins involved in frontotemporal dementia (FTD) and the research being done at at the University of California San Francisco (UCSF) on these proteins.  Genetics are also addressed in this article.

In FTD, 40% of cases involve tau (which is also part of PSP, CBD, and Alzheimer’s Disease), 50% of cases involve TDP-43, and 10% of cases involve FUS.  There is a genetic component to about half of all FTD cases.

Dr. Bruce Miller at UCSF’s Memory and Aging Clinic comments on how to find those with FTD who are early in the disease course:

“What is so fascinating about this is, what do you define as ‘affected’ in somebody who carries a gene that is going to cause a slow, subtle social decline? What are good markers for someone who is starting to get sick? Addictive behaviors ­ drugs, alcohol, gambling ­ bad decision-making, alienation of other people around them. These are things that we never realized could represent the first symptoms of a degenerative disease.”

Here’s a link to the full article:


May 5, 2012
The New York Times
Studies Tie Abnormal Protein Buildup to Dementia
By Denise Grady

A few excerpts are copied below.



Excerpts from

Studies Tie Abnormal Protein Buildup to Dementia
New York Times
By Denise Grady
May 5, 2012

Scientists think that abnormal protein deposits inside brain cells
cause frontotemporal degeneration. The proteins vary, but they do not
include amyloid, the substance found in Alzheimer’s patients.

In about 40 percent of patients, the deposits are an abnormal form of
a protein called tau, which normally gives structural support to brain
cells. (Tau is also one of the proteins found in Alzheimer’s

Two other types of deposits are abnormal versions of proteins involved
in other cell functions. In about half of all patients with
frontotemporal dementia, the protein is one known as TDP-43, and in
about 10 percent it is a substance called FUS.

But why do these protein deposits form? Often, the underlying reason
is not known.

At least half of all cases are sporadic, in people with no family
history of the disease and no known genetic disorder. About 40 percent
of patients do have a family history, and some may have an
identifiable genetic mutation.

In the remaining 10 percent…the disease is definitely inherited: a
dominant gene makes the symptoms inevitable, sometimes as early in
life as the 30s or 40s, in anyone who inherits a copy from an affected
parent. And each child of an affected parent has a 50-50 chance of
inheriting the bad gene.

So far, most inherited cases have been linked to mutations in two
genes, both on the same chromosome, number 17. One gene codes for tau.
The other gene codes for a protein called progranulin and causes a
deficiency of it, which appears linked to the buildup of TDP-43. Three
other genes are involved in some cases, and researchers are looking
for still more.