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 Looking at enzyme levels in CSF to diagnose DLB 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Looking at enzyme levels in CSF to diagnose DLB
These Italian researchers are looking for a biomarker for DLB, AD, and FTD. In this study, they measured the activity of several enzymes in cerebrospinal fluid on those with clinical diagnoses of DLB, AD, or FTD, and healthy controls. They found that "beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies." "Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies" including PD and DLB.
Robin


Neurobiology of Disease. 2009 Mar 19. [Epub ahead of print]

Cerebrospinal fluid beta-glucocerebrosidase activity is reduced in dementia with lewy bodies.

Parnetti L, Balducci C, Pierguidi L, De Carlo C, Peducci M, D'Amore C, Padiglioni C, Mastrocola S, Persichetti E, Paciotti S, Bellomo G, Tambasco N, Rossi A, Beccari T, Calabresi P.
Section of Neurology, University of Perugia, Italy.

The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely beta-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes - alpha-mannosidase (EC 3.2.1.24), beta-mannosidase (EC 3.2.1.25), beta-glucocerebrosidase (EC 3.2.1.45), beta-galactosidase (EC 3.2.1.23) and beta-hexosaminidase (EC 3.2.1.52) - in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies.

PubMed ID#: 19303930 (see pubmed.gov for this abstract only)


Tue Mar 24, 2009 7:10 pm
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Joined: Tue Feb 06, 2007 8:35 pm
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Location: Toronto, Canada
Post Test for family members?
Hi, Robin,

Do you know of any diagnostic tests/examinations that mignt be available in North America for predicting possible development of LBD in offspring of those afflicted with this dementia? I am now 57 y.o. My mom was diagnosed at 79 years of age, but in hindsight, we can see that there were earlier symptoms of LBD for which she compensated well.

How significant is the consumption of copper, and other metals, toxins, monosodium glutamate, and whatever in the early onset of LBD in those who may be genetically predisposed? (Forgive me, but I am thinking along the lines of phenylalanine ingestion in susceptible babies and mental retardation.) Are there enzymes one can take to preclude getting LBD?

When you get a chance, I'd appreciate your itemizing any and all substances you think LBDers' offspring should avoid/consume in order to keep LBD at bay for as long as possible. I have three brothers and one sister and we are all terrified of getting LBD. I went to visit Mom in hospital two weeks ago and I could hardly believe the change in her since late May. :(

I share with my siblings and their partners all my info gleaned on the forums. They appreciate it.

Thank you for all you do for us on this forum. :)

- dale

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Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Mon Apr 06, 2009 3:10 am
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Hi Dale,

There is no genetic test for LBD. There is lots of genetic testing that kind of skirts around LBD. For example, you can be tested for APOE4, which has some association with AD. (Not everyone with APOE4 will get AD.) Or you can be tested as to whether you have the alpha-synuclein gene, LRRK2. That's basically a test for familial PD. (I don't think everyone with LRRK2 gets familial PD...but the percentage is very high.)

If you have a blood relative with an LBD diagnosis, you could consider having them receive the genetic testing. Counseling is required prior to the testing. And counseling is required for any blood relative who wants to know the results.

A plug for brain donation seems appropriate here. It's the only way to know with certainly what the diagnosis is.

I don't think we know really anything about the causes or possible causes of LBD. My impression is that we are far away from doing that research in any serious way. There's quite a bit of research into the causes of PD, and perhaps that's related to the causes of LBD.

I know of nothing (enzymes or otherwise) anyone can take to prevent getting LBD. The NIH is looking into a variety of substances which may be neuroprotective against PD. Examples: CoQ10, creatine, some antibiotic (minocyline??). There is also some thought that Azilect (rasagiline) may be neuroprotective.

I'm sorry I don't know more. You have reached the limits of my knowledge on most (all?) of these topics!

Robin


Wed Apr 08, 2009 12:28 am
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Joined: Tue Feb 06, 2007 8:35 pm
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Location: Toronto, Canada
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Thank you, Robin, for sharing your knowledge, which is vastly greater than mine! I am very grateful. Yes, I will be urging the family to donate dear Mom's brain for research. I may suggest genetic testing on Mom and genetic counseling to the rest of the family. Not sure how that will go over. Right now everyone's nerves are still raw from Mom's rather abrupt down slide this past January.

What's your take on the enzyme treatment for Gaucher's disease possibly helping prevent LBD? Aren't the two somewhat related in terms of defective enzyme, glucosylceramide beta-glucosidase?? Just how hard would it be to get treated for Gaucher's disease if one suspects/fears developing LBD down the road? What's the diagnostic test for Gaucher's called?

Mom mentioned a while back that she had an uncle whom everyone thought "went crazy" toward the end of his life...sounds like LBD. :?: Mom was a teen when he died. Her bloodline is British/Scotch with some native North American Indian.

btw, would you say that restless leg syndrome might be a predictor for developing LBD? I sometimes get RLS but find I can treat it myself with B-50 + Folic acid complex and more rest.

I know you're trezzz busy, so when you get a chance, I'd appreciate your thoughts on these questions. :?:

Thanks again,
- dale :shock:

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Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Wed Apr 08, 2009 2:48 am
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
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Dale,

You're really stretching me to the limits! And I'm not sure I know more about this than you do...

Gaucher's has come up several times in looking at LBD. I'm not sure I've posted everything here because I assume few, if anyone, is interested. This recent abstract was especially interesting: PubMed ID# 19286695. There is a test for the GBA genetic mutation. I don't know how Gaucher's can be treated or if it can be treated (I assume not). The two best sites for basic medical disorder info are emedicine.com and the NINDS site (ninds.nih.gov, I think).

I would *not* say RLS is a precursor to LBD. On the other hand, RBD is very often a precursor to LBD, MSA, or PD.

If your mother has a PD diagnosis, or ever had a PD diagnosis, you can sign her up for genetic testing for $25. See:
http://michaeljfox.org/23andme.cfm
Last month, 23andMe allowed those in our local support group to sign up -- these are patients with atypical parkinsonism diagnoses -- but that window has now closed. 23andMe is exclusively focused on PD; the goal is to sign up 10K people with PD. At this time, family members are not allowed to participate in the $25 genetics testing.

I wouldn't try to convince an entire family of the wisdom of any of this. Just convince the spouse or the healthcare POA. Much better to have the info available (ie, the genetic testing done and the brain donation done) such people can access the info later, if they choose to.

Robin


Wed Apr 08, 2009 10:14 am
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Joined: Tue Feb 06, 2007 8:35 pm
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Location: Toronto, Canada
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Thanks, Robin. No, Mom never got any diagnosis other than LBD, but I know she suffered some involuntary arm movements earlier on (couple of years ago) that have now subsided without levodopa or any PD drug intervention. The only meds she's been on are galantamine and now low dose seroquel for the disturbing hallucinations and aggressive behaviour (she threw a paper cup of water at a nurse) and is very uncooperative in general with them. She's developed shingles and is very sensitive to any touching, ergo the uncooperativeness with nurses. She has her good days when she's an angel still. I just hope she'll be kept as comfortable as possible. Family in NB visit her often. I'm tied to a fulltime (evening) job and can't get home as often as I'd like due work restrictions and expense of flying.

Thanks for all your interesting info. You really are as well informed as anyone can be given the state of the research at present. Many thanks!
- d.

_________________
Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Wed Apr 08, 2009 12:46 pm
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