News from our SFO Meet-up

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Julie G
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News from our SFO Meet-up

Postby Julie G » Sat May 30, 2015 1:02 pm

I'll break the ice and start a thread that I hope all will contribute to...

I must start by sharing Rep's hilarious analogy of our meet-up. We broke all of the rules; you know, the ones you give your kids. We talked to "strangers" on the Internet in a secret chat room: apoe4.info. We arranged a meeting and then (some of us) shacked up for a few days. It could have gone horribly wrong, but instead it went brilliantly.

The experience of spending time with our members was equal to the experience of being in the presence of (and learning from) legends in our field. Everyone was lovely and our presenters were incredibly generous to us. IMHO, none of what we learned was contradictory or mutually exclusive- very good news for us. By combining multiple approaches, many of us may have the opportunity to be skateboarding into our 90s, with all of our lights on :D

I'll post more as I'm able. I know other will do the same.

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Re: News from our SFO Meet-up

Postby KatieS » Sat May 30, 2015 3:09 pm

Thanks to Julie, we were able to meet with founders of E4 research at Buck and Gladstone. I've delayed posting while trying to find my notes.
Dr. Bredsesen- His filling the "36 holes in the roof with multiple supplements, sleep, diet and exercise may soon have more objective follow-up proof , beyond the initial documented AD , then post-intervention improved RTW/neuropsych testing. He will be doing follow-up retinal amyloid scans on these cases. It's expected that within this next year, these retinal scans will be commercially available to us. Another dilemma as to whether is get the scan. He is developing big data systems with Muse Labs so his personalized prescription can be widely available.
Dr. Krauss- Unpublished results appear to be pointing that medium and large size LDL is associated with amyloid, however the small LDL is strongly linked with cardiovascular disease. He firmly states that high LDL-P should be treated with statins because the cognitive side effects occur in a limited subset and dietary/lifestyle changes will not decreased the LDL-P enough. I'm not sure I heard his reply clearly as to the benefit of hydrophilic statins vs lipophilic statin, other than he does not think statins increase AD.
Dr Mahley & Dr. Huang- Representing over four decades of E4 research, they believe E4 is the cause of AD via resulting from the head to tail compression of E4. As you will recall Gildamesh's avatar of the compressed E4, this structure more than the less compressed E3, allows the head and tail to hit. Their first goal is to develop a structure corrector of E4, stretching it out to more like an E2. Stavia aptly replied to call it an E1. Studies are looking favorable in female mice. However, they are going to continue to attack the E4 downstream with protease inhibitors and injecting regenerative stem cells. Possibly within this next year, you would be able to measure these toxic fragments in a blood test. Many risks such as depression or head trauma increase the fragmentation levels. Mer commented on this exciting blood test to feedback our preventative measures such as the ketagenic diet or various supplements.
I'm sure there is much more to add…
Last edited by KatieS on Sat May 30, 2015 7:56 pm, edited 1 time in total.

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Re: News from our SFO Meet-up

Postby Stavia » Sat May 30, 2015 5:59 pm

Just got home, jetlagged, but will summarise my notes quckly as I know you are all waiting
1. The connection between the members in the flesh was beyond expectations. The members who could not be with us were close in our thoughts at all times.

2. Julie spoke magnificently at the Buck meeting. She spoke with eloquence and passion and sincerety. They loved her.

3. Dresedens speech told far far more than his paper. At lunch he said that it was difficult to pack enough detail into a few published pages. We also met with his top scientist Dr Ram Rao who took us through the science. The talk was videoed and we hear that it will be on the Buck website at some stage. Basically the premise is that there is an interaction with apoe4 and pro inflammatory mediators such as RelA which tips the system towards a pro inflammatory state in which NFkB is dominant and SirT1 inadequate. This causes neurones to degenerate. Apoe4 does this by entering the nucleus and binding to 1800 gene promotors. They have grouped the effects into his programme's 36 "holes" which they are trying to plug thru their various modalities.
This is the MEND programme. We have a handout that we will give you.
I can't upload it from my phone.

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Stavia
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Re: News from our SFO Meet-up

Postby Stavia » Sat May 30, 2015 6:12 pm

4. Dr Kraus spoke about the huge uncertainty of the role of lipoproteins in apoe4 as the trials just simply aren't there. He also couldn't give us targets as again the trials just aren't there.
What he could say with certainty was that lipoproteins matter in the absence of IR. Saturated fat should be less than 7% of calories. Saturated fat is a problem with us because we start at a higher LDL than other folks and the sat fat downgrades the LDL receptors thus slowing clearance and large LDL accumulates. Butter and red meat are bad. Milk and cheese neutral. Carbs bad if IR is present and too many small particles.

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Re: News from our SFO Meet-up

Postby Stavia » Sat May 30, 2015 6:19 pm

5. Gladstone Institute. They are developing a molecule corrector.
Dr Robert Mahley was one of the discoverers of the apoe proteins. They initially thought there were four but apoe1 turned out to be mislabelled glycosylated apoe3 (or 2. cant remember ). He has been working on apoe4 for 40 years, 20 of them with Dr Yadong Huang.
Together they have a different hypothesis, in that the apoe4 molecule is fragile and fragments easily through a process called proteolysis, and the fragments are neurotoxic. Tau and its phosphorylation is a major player here. Their vision is for a drug molecule that binds to apoe4 and changes its shape so as to make it more robust.
They have developed an assay which measures the fragments in the blood.
They are at the stage of mouse models and have had some success. However we are some years away from a drug if they are successful.

They have a plan B which would be a protease inhibitor. This has been worked on a bit. Plan C is extremely speculative and would involve mitochondrial protection.

Image

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Re: News from our SFO Meet-up

Postby Stavia » Sat May 30, 2015 6:28 pm

So finally my overall feelings: and they are only mine.
1. Our members are awesome. 11 of us shared one working shower without a grumble.
2. Julie is very smart and I am delighted to discover she is very funny.
3. We are a formidable think tank and we need to continue to work together collaboratively
4. A drug is at least 5 years away. I tend to be conservative so I am thinking 10 years.
5. Therefore we need to focus on prevention. I personally don't care if its amyloid or tau or pixies. We know the things that can shift the balance. Dr Bredesens protocol is pretty much a sophisticated version of the framework we worked out ourselves. Its by far the best Ive seen out there. I will be slowly working my way through its strategies and implementing them

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Re: News from our SFO Meet-up

Postby bentkat » Sat May 30, 2015 7:30 pm

Thank you for posting your notes. Wish I could have joined the group. Catch up on your sleep; that is important for us E4's.



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Re: News from our SFO Meet-up

Postby Stavia » Sat May 30, 2015 8:00 pm

This is George's excellent synthesis from the original thread.
I am copying it here:

GEORGE says : "Kudos to Julie to putting together a stellar lineup of fantastic speakers. She also did a spectacular job addressing a packed audience at the Buck, prior to Dr. Bredesen's talk. Also thanks to Julie, not just for the yeoman's work of putting this together, but also for her personal touch that made these connections with these awesome investigators possible. All of these very high-powered researchers were anxious to meet and talk with us, thanks to Julie. Also thanks to Stavia for her personal touch, creating connections on the fly, that will pay many dividends in the future. Quick notes: Julie did a wonderful job on her talk and creating a connection for our group. Bredesen's talk was very much like the one previously linked here that he gave to the California State legislature a few weeks ago. There is a handout that I'm sure someone will scan and post here on his tweeks to his protocol (we're on holiday for another week). Bredesen told me he's working on a book to tell everyone how to do this on their own- how to order tests and get supplements. No mention of when it might be done. Dr. Krauss was very interesting but no clear cut guidelines for us. Asked about an appropriate level of LDL-P for us and he said 1,500, 1,200, 1,000 or less might be appropriate, depending on the individual. My opinion is that serial EBT calcium scans https://www.apoe4.info/forums/viewtopic.php?f=5&t=1355&hilit=EBT are the best way to answer the heart disease question. Drs. Mahley & Huang presented their work. In a nutshell, the neuron expresses ApoE for repair, in response to an insult. It can see the differently shaped 4 protein as a problem and attack it (this can also happen to 3, but much less frequently). As a result there are protein fragments that can build up. Quantities of these fragments are correlated with cognitive decline. They are working on a fragment assay. They are working on molecules to fix the shape of the ApoE protein so it won't be attacked. This work as been done in mouse models. The body can clean u fragments if the clean up mechanisms aren't overwhelmed by new fragments. They are working with a venture capital investment group to create a startup to take the testing and molecules to the next step. They are very close to launching. The CEO chosen by the venture group to make this happen, Leon Chen, also addressed us. He is a PhD scientist with a B-School degree who has done this numerous times. He is very impressive. Mahley discovered the E4 gene. When asked where is the E1, he said, that was a mistake, we thought there was an E1, but it turned out to be a glucose saturated E2. There is no E1"

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Re: News from our SFO Meet-up

Postby Julie G » Sat May 30, 2015 9:48 pm

A few more impressions... Bruce & I got into CA late the first night so we stayed in Novato to be near The Buck and sadly missed out on meeting everyone in the Berkley commune. The next morning, driving up and seeing the gorgeous rolling landscape, resplendent with grazing cows and deer was magnificent; then the madly impressive I.M. Pei architecture of the building itself came into view. Despite the grandeur of the modern angled building gleaming with imported travertine limestone, it nestled right into the Marin County landscape. It truly looked like a movie set. We finally began our ascent up the front sidewalk. The enormous glass doors suddenly burst open and Stavia, cute as a button with the energy of a tornado, ran at least 6.5 mph and tackled me in a major bear hug. Pure happiness and tears.

We walked into the stunning lobby and I finally got to put names with faces- very exciting. It truly felt like be reunited with family members. It was especially wonderful to meet our 78 y/o homozygote matriarch (and my role model) Starfish, who had zero problem keeping up with the group and attended every single event- no easy task as we traversed the whole Bay Area. (Of course, she drove herself 8-) ) Within minutes of meeting sweet George, he was performing myofacial release techniques on my shoulders in the lobby of The Buck to loosen me up for public speaking- argh. He pushed a certain spot and my tension truly melted away. See the funny pic below. Many folks in the house got to benefit from his mad skills. We have lots of photos of the events, but unfortunately won't be sharing due to privacy concerns. A professional video of the talks at The Buck will eventually be shared with all. George taped our meeting at CHORI, but Dr. Krauss wanted to go off-record on a few comments (camera off) and he spoke softly- not sure of that video quality.

Speaking of privacy concerns, during my talk I invited members of our group to stand and be recognized if they so desired. I saw a few head shakes and disapproving looks from them. I was fully prepared for no one to stand, but was stunned when they eventually ALL stood up in a wave to thunderous applause. Afterwards, I asked them WHY they stood. Stavia replied, "We couldn't let you stand alone." Lump in my throat moment. There were lots of them. More tomorrow...

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Re: News from our SFO Meet-up

Postby Russ » Sun May 31, 2015 5:49 am

Just saying it simply... you folks are all awesome :-).

Truly wish I could have been there. I expect we will all benefit not only from the many insights gained by the many that were able to make it, but the seeming energy you passed on to the researchers about our interest in their work. Sounds like the scientists and physicians must have found the whole experience very rewarding as well. Can't wait to see progress further accelerate with passion of the citizens, scientists and doctors all working together to shape a new paradigm for brain (and heart) health that recognizes both our commonalities and our differences.

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