Genetic testing for Pick's Disease

June 27, 2015 11:27 PM

Two part question. First - my family strongly suspects my father has late-stage Pick's Disease, which is a form of fronto-temporal dementia. It can't be truly diagnosed until an autopsy though. He's post-65. He has most of the symptoms. So I have two very related questions.

In doing research about this I'm finding conflicting information about if it is hereditary or not - some articles say no genetic component, some say yes, one very alarming one says a strong genetic component.

Does anyone know more? I'm not sure what articles to believe!

If there is a genetic component, is there testing for it? Is it a good idea to get tested? I have no idea, and I don't know where to start.

posted by anonymous to Health & Fitness (5 answers total)

My sympathies, neurodegenerative disorders really suck.

In case you aren't familiar with Pubmed, which is a great resource to search through primary peer reviewed literature, here's a recent 2014 free open access review paper on the subject:

Frontotemporal dementia and primary progressive aphasia, a review.

FTD is now one of many “tauopathies.” In particular, the tau mutations are seen most commonly in the bvFTD cases and the progressive non-fluent type of PPA. Seelaar et al65 reported that, in a series of 364 patients with FTD, 27% had positive family histories suggesting autosomal dominant inheritance. Of these, 11% had tauopathies secondary to mutations of the MAPT gene on chromosome 17.

The majority of cases of FTD, however, are not associated with tau pathology or mutations. Most of the remaining cases have been noted to have ubiquitin immunoreactive inclusions in the cytoplasm or nucleus, or ubiquitin immunoreactive neurites.

To summarize the breakdown of specific FTD syndromes with these molecular genetic disorders, most familial cases of PNFA have an MAPT mutation. Semantic dementia patients mostly have ubiquitin inclusions, associated with progranulin mutations. The logopenic variant of PPA usually has neither tau nor ubiquitin accumulation, but rather represents a focal presentation of AD. On the other hand, apolipoprotein E4, which is associated with an increased risk for late-onset, sporadic AD, does not appear to be of increased frequency in FTD or PPA patients.

To summarize, to answer your specific question, it's not known with certainty whether there is a specific genetic defect that is associated with the symptoms of Pick's disease.

Pick's Disease is a name given to a group of symptoms. Lots of different things can go wrong that lead to similar symptoms. Not all people diagnosed with Pick's Disease have the same genetic difference (compared to people who have not/will not develop PD). Not all people with the same genetic difference will develop PD.

Tau (transcribed from the MAPT gene; MAPT is the name for the gene that is responsible for the Tau protein) is an ubiquitous protein in neurons that associate with the cellular scaffold that determines the shape and mobility of neurons.

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As for genetic testing, there are lots of companies/services who are willing to fleece you. I will not mention their names since googling "genetic test" will bring up one of the worse players.

The "genetic test" for Tau/MAPT mutations is trivial - just sequence your MAPT gene. The hard part is interpreting whether any differences/similarities of your MAPT sequence is indicative of your susceptibility to FTD.

It's simply not currently known.

Feel free to memail me (or discuss it here) if there's anything I could help explain.
posted by porpoise at 1:22 AM on June 28, 2015 [1 favorite]

First, I'm so sorry about your father. Pick's is a relentless disease that leads families through a wild ride. My sister was diagnosed with Pick's at age 53. There are several types of FTD. Pick's Disease is usually the behavioral variant of FTD (bvFTD)-not PPA mentioned above. The Association for Frontal Temporal Degeneration (www.theaftd.org) has a ton of information which may be helpful.

Most cases of Picks are not genetic. They really don't know where it comes from. No one in my family has ever had any type of dementia, much less FTD. The first time my sis's neurologist met my sister's daughter he told her it was not genetic.

It can be diagnosed with a brain MRI showing atrophy of the frontal lobe and a test by a neuropsychologist which would show a deterioration in executive function.

There are several FTD groups on Facebook. Many are very helpful. Feel free to message me if you have further questions.
posted by Jandasmo at 5:45 AM on June 28, 2015 [1 favorite]

When my mother died, she also had some dementia.
Our doctors said that they didn't really know what type, and testing the rest of the family was kind of useless without knowing the exact type. But we were able to test for cancers.
posted by littlewater at 9:33 AM on June 28, 2015

I'm sorry to hear that you're going through this. This all sounds super overwhelming, and there's so much information out there it's hard for anybody to know what to believe!

The Merck Manual and UpToDate for patients are both reliable sources of information.
posted by gemutlichkeit at 1:22 PM on June 28, 2015

There are many states that allow a certified genetic counselor to see you for a counseling appointment (i.e., without linking it to a doctor visit). They would be the best resource for letting you know what hereditary neurological disorders for which there is currently legitimate testing.

This is the National Society of Genetic Counselors "Find a Counselor."
posted by kuanes at 3:36 AM on June 29, 2015