March 13th, 2014 -- It’s already been a year. FTD/PPA explained.

March 13, 2013 about 3am – Mom had finally had enough of FTD/PPA and let go.  Today is March 13th, 2014.  I can’t believe it’s been a year.  On November 3rd, our grandmother “Nanny” also had had enough of FTD and took her place with Mom. 

While I think my entire family is thankful 2013 is over; we are thankful Mom and Nanny are finally “whole” again and at peace and “we are thankful for everyday we've had with them and every day wont – bc that is one less day they are suffering.” 

While this is all true, it is independent of how much we miss them both.  Too often, I find that I have forgotten, and I pick up the phone to call my mom and tell her news, and then reality hits.

Breath gone, stabbing pain in the chest, stinging in the eyes.

Tomorrow – March 14th, I will turn 30, and Mom won’t be there.  One day I hope to get married and I’ll have to go wedding dress shopping without her.  My kids will never meet her.  

It’s not fair.  

But no one ever promised life would be.

I smile at this because I can hear my mom’s voice.  So many times growing up, I would want something and she would say no, and I would say it’s not fair and her response would be, “Tough.  Life isn’t fair.”
So yes, today is one year from when Mom let go.  It feels like yesterday and it hurts just as much today as it has for the last 6 years.  But, I have two choices.  I can cry about it (which, trust me, I have and will some more) or I can do something about it.

Our family chose the latter. 

As you all likely know by now, our family is hosting a Memorial Benefit on April 26th, 2014 (See EVENTS tab above for details).  Last year, with your help, we raised over $5,000 for The Bluefield Project to cure dementia.  Our goal this year is to exceed that.   We’re off to a good start—check out the donation tracker to the right!

If you have been following this blog, you know it was FTD that my mom and nanny had.  And you also know that it is genetic. 

However, if we are going to ask you to support/attend a Benefit (which will be lots of fun so you should definitely come!), I think it is fair I take a pause and explain some science behind FTD and more importantly – why do funds go to the Bluefield Project.

Bottom line:  Bluefield Project and the CFR= hope.  They focus on the genetic FTD our family is inflicted with—with they believe will that the findings will have parallel benefits to other neurodegenerative diseases, including Alzheimer’s, ALS, and cerebral traumatic encephalopathy – which is only now receiving attention in the area of contact sports.

Keep reading for a little genetic FTD 101 lesson. In advance, thanks for listening J (Sources for the below: a mix of U of Penn, Bluefield Project, Alzheimer’s Association and The AFTD)

What is FTD?
FTD used to be referred to as “Pick’s Disease.”  Today, Frontotemporal degeneration (FTD) refers to a family of disorders characterized by the progressive loss of neurons (brain cells) in the frontal and temporal regions of the brain.  Although the precise cause is unknown, FTD is thought to result from abnormal accumulation of misfolded proteins, which disrupt, and eventually kill, brain cells. 

What are early signs/symptoms?
Patients with Frontotemporal degeneration can present with different clinical symptoms, ranging from behavioral impairments to language or motor dysfunction.  Mom and Nanny were first language impairment and eventually motor dysfunction as well.

If you had to describe FTD in one sentence, what would it be?
FTD strips you, in your prime (40-60yrs, typically) of everything that makes us human -- insight, empathy, communication (ability read, write, understand), and sometimes personality.  

Is it treatable?
No, as of now, FTD is fatal upon diagnosis.  There is no treatment or cure.  There are some drugs that help ease symptoms, but nothing to actually treat the FTD.

But I've never heard of FTD - it must be rare.
Actually, it's not. It's the second most common form of dementia for younger generation-- even more common than Alzheimer's -- it's just often mis-diagnosed as depression/anxiety/Alzheimer's or not diagnosed at all.  With awareness and education, more and more cases are being discovered.

What are the different subtypes of FTD?  
Type of FTD
Clinical Description
Description of Possible Symptoms
Type of Pathology seen in Brain
behavioral variant FTD (bvFTD)
Changes in Personality, emotions and/or behaviors
- Hyperal (ex: eating only sweets or a certain type of food)
- Disinhibited actions (ex: making inappropriate comments)
-Apathy, lack of motivation to do things
-Lack of Insight (unaware of the impact of symptoms on others)
-Impaired decision makings
- Associated with the Tau or AD pathology
primary progressive aphasia (PPA) (nonfluent varient, semantic variant, and logopenic variant with subtle differences)
Deterioration in the ability to produce speech, understand words and recognize objects, ability to retrieve words in speech
- Hesitant, effortful speech
- Difficulty naming objects or recognizing the meaning of words
-Difficulty recognizing familiar objects or faces

- Nonfluent - most often linked to the tau protein; 
- Semantic - most often linked to the TDP-43 protein
-Logopenic - Most often associated with Alzheimer's (AD).
Corticobasal Syndrome (CBS)
Involuntary movements and/or cognitive dysfunction
-Apraxia ro difficulty w/ use of tools
-Executive or social deficits
- Cognitive problems such as simple math and difficulty with spacial orientation.
Tau or AD associated
Progressive Supranuclear Palsy (PSP)
Deterioration of gait and balance
-Hallmark feature is inability to move eyes up and down.  
- May also have other FTD subtype symptoms
Tau Protein
FTD with Amyotrophic Lateral Sclerosis (ALS)
Same changes seen in other subtypes of FTD accompanied by deterioration of the motor neurons
-Any symptoms associated with bvFTD or PPA
-muscle weakness and atrophy
-muscle cramps
-difficulty swallowing
-slurred/muted speech
TDP-43 Protein

What did Mary have? 
Both Mary and her mother (as well as our Uncle Steve, great grandmother and great great grandmother), have the FTD linked to the TDP-43 Protein.  Mom and Nanny both showed symptoms of the PPA subtype and FTD with ALS (commonly known as Lou Gehrig’s disease) subtype.

If it’s genetic, what are the odds of passing it on?
It's 50% (but I think "100% or 0% is more accurate).  For the subtype our family has and the subtype Bluefield Project has started clinical drug trials -- it's like brown eyes - it's a dominant gene that we were either born with or do not have at all.  

Let’s have a short science lesson, shall we??

Genetics 101:  Our genetic material, DNA, is stored in every cell of our body.  DNA chains are then packaged into larger units call chromosomes.  We have 46 chromosomes.  They come in pairs and in each pair – one is from our mother and one is from our father (22 pairs are “autosomal” and the 23rd pair determines our sex).

Genes are specific segments of DNA that carry the instructions for making proteins.
Proteins are molecules made up of a chain of amino acid building blocks.

Proteins are used by the body for maintain its structure and function.  Because our cells have two copies of every autosomal chromosome, this means we have two copies of each gene.

Remember this for later:
A mutation is a change in the DNA sequence; in other words there is a “spelling mistake” or typo in the instructions to make a protein.  So when there is mutation, that copy of a gene has the wrong instructions and so it makes a protein that does not function correctly in the body or is not produced in sufficient quantity.

(It is important to note – not every change identified in the DNA is automatically considered to be a disease-causing mutation.  Some are not harmful at all, but instead normal variations in the genetic code.)

So, what does that have to do with FTD?
Most cases of FTD are sporadic—no known family history.  But in some cases it is not.  See the below chart – our family is in the yellow.

A few terms: 

“Hereditary” indicates that a trait or disease can be directly transmitted between parent and offspring.
“Familial” is a very broad term used to indicate that more than one person in the family has a train or disease.  Familial denotes that there is a possibility of a genetic cause.
Now, remember “big R” and “little r”” from school? 

R = autosomal dominant.  “Autosomal” as noted above, means it’s from the 22 pairs of chromosomes that are identical in both males and females.  So both genders have an equal chance of being affected if a mutation is present on a gene in an autosomal chromosome.  “Dominant” inheritance means that only one copy of the gene has to have a mutation to cause the disease.
That’s where the 50% comes into play.  Dad has two “good” genes.  Mom has one mutated and one good one (remember, they come in pairs).  The mutated gene is big R in the box. 
We (the offspring) got a little r from our father since he has two little r’s.  There was a 50/50 shot that we got the little r from our mother.  If we got the little r, the mutated gene does not exist in us, we cannot pass it on.  “Skipping generations” is a myth.  Two little “r’s” = no mutation.
But If we have inherited the big R, we will eventually be diagnosed and now also have a 50/50 shot of passing it on. 

What is the mutated FTD gene called?
  • There have been a few mutated genes discovered, but to keep the conversation specific to our family, it is GRN.
  • GRN was only discovered in 2006 (mom was diagnosed in 2008). GRN codes for the protein “progranulin.”  Individuals with GRN mutations have abnormal accumulations of the TDP-43 protein in affected neurons.
  •  Average age of onset is 59 years—Range is 35 years old to 87 years old (Mom was 56, Nanny was 80).   
  • Why the age difference, you ask?  This will be discussed in a future post—this is a mystery that is still unraveling!

What does not having enough progranulin protein have to do with FTD?
Why not having enough progranulin causes frontotemporal dementia is unknown, but it’s the question driving research in frontotemporal dementia labs around the world. Progranulin is involved in a diverse range of biological processes including inflammation, tumorigenesis, development and wound repair. It is widely expressed in most tissues in the body, but it’s not necessary for life. Model animals, like mice and worms, can live and reproduce even without progranulin. Why loss of progranulin seems to preferentially impact the brain even though it’s involved in a host of processes is unknown.

What does loss of Progranulin do to brain cells?
The end result is that loss of progranulin causes brain cells to die. (And then literally, the brain shrinks). We don’t understand how this happens, but this is one of the major research focuses within Bluefield and the CFR. Recent data suggest that loss of progranulin results in an abnormal immune response in the brain – researchers are working to understand how this might cause neuron death.

You mentioned ALS?
Yes, ALS is also a form of dementia.  While ALS can exist on its own as well, research has confirmed links to certain FTD subtypes and ALS.  And the TDP-43 is one of the links.  (I will discuss this more in a later post as well).

AND FINALLY, who is the Bluefield Project/CFR and why should I donate anything toward them?
  • As noted above, the Bluefield Project = Hope.  REAL HOPE.    If there is any silver lining to having hereditary genetic disease, it’s the Bluefield Project.
  •  It’s tough to find a treatment or cure when you don’t even know the cause.   But the cause –  TDP-43- is known in my family’s case.
  • The Consortium for Frontotemporal Dementia Research (CFR) was established in 2008 by the founders of The Bluefield Project. Its mission is to find a treatment or cure for frontotemporal dementia though systematic collaboration of best-in-class scientific investigators.
  • Bluefield Project is based out of UCSF and manages a consortium of 16 principal investigators at nine Universities, who are funded to pursue research into the genetics, biology and translational research of the disease.  This includes international institutes as well.  In other words—they are SHARING information and COLLABORATING instead of keeping their research a secret and competing, which is so often the case in research. 
  • They are 5 years into a 10 year mandate to find a treatment or cure for FTD.
  • HOPE:  Led by a team composed of the highest caliber basic scientists and renowned clinical neurologists, with an aggressively funded research agenda and a unique research model, the CFR firmly believes that a cure for frontotemporal dementia is possible. 
  • Based upon the research they have supported, the first clinical trial with a drug to treat FTD was initiated in 2013. Recognizing that they do not have the funds to take a drug through registration trials, they have focused on using their research and translational science to identify a handful of potential targets in FTD, along with a number of drugs that engage these targets.
  • Bluefield Project was founded by a family (from Bluefield, Virginia) with the same genetic FTD who decided to do something about it.
  • Bluefield believes that the findings they have made in FTD will have parallel benefits to other neurodegenerative diseases, including Alzheimer’s and ALS and cerebral traumatic encephalopathy - which is only now receiving attention in the areas of contact sports.

In Conclusion,
There is hope and our family will do everything we can to help.   I'd like to share what my brother, Adam wrote today:

"PPA is cruel, there is no treatment, no preparing, no numbness, and the progression is just slow enough it challenges every bit of faith in a god you have. 

Not only did she have to watch herself die, but watch herself lose herself. We couldn’t say goodbye because it was too early, she couldn’t say goodbye because it was too late.

When I put my children to bed and the room is quiet, I think to myself I am grateful they are too young to remember the suffering, but it breaks my heart they will never feel the comfort of her presence and the reassurance of her voice. I know I will never be the parent or person that she was, nobody will. We can only keep her memory alive and strive to live up to her example. 

Maybe with enough awareness, the next grandmother will be able to tuck her grandchildren to bed.

I love you mom."

Mom’s mantra was “Deeds not words shall speak me.”  Mom always put herself second and family, friends and the community first.  It’s time for us to carry on her mantra. We are so quick to share funny pictures and stories on facebook/twitter etc.  Please consider sharing this post and supporting the fight against dementia by supporting Bluefield research by clicking here.  

Each and every one of us can tell a story about someone with dementia.  They never gave up on us, let’s not give up on them.

Thank you for listening.

Mom, Nanny – we love and miss you both.

~The Halls~

(if you would like to read more or have a concern about a loved one: UCSF has great information at )