Peter Davies Observes
Transcripts of Dr. Davies' live commentaries from Amsterdam.

19 July 1998. Peterdavies enters. Peterdavies says, "Hello!" Peterdavies applauds fervently. Peterdavies apologizes. Peterdavies throws its head back, cackling with glee. Peterdavies attempts to calm itself. Peterdavies begs like a dog. Peterdavies capers around. Peterdavies chortles demonically. Peterdavies chuckles in amusement. Peterdavies bows gracefully. Peterdavies leaves.

Newperson enters. Newperson boggles at the concept. Newperson begs like a dog. Newperson says, "Hello, is anybody there?" Newperson cowers in fear. Newperson swirls itself around the room, dancing. Newperson says, "Hello, this is a joke. :))" Newperson curtseys demurely. Newperson leaves.

Jcv enters. Jcv leaves.

Martha_merton enters.

Peterdavies enters. Peterdavies says, "Hello from Amsterdam, it's Sunday Night"

Martha_merton says, "The support plug-in is in place"

Peterdavies says, "This is a rather large and difficult meeting to manage. Aside from the three plenary lectures this morning, all the other talks are in sessions that run four at a time. It is a little difficult to be in 4 places at once. The poster sessions are particularly well organized, in that they surround a free lunch. This means that everyone is guaranteed to be in the poster area, and this promotes a great deal of exchange of information."

Peterdavies meditates.

Martha_merton says, "Is this a new research method?"

Peterdavies says, "It would be a real asset to the field if more of the players spent time in meditation. On the other hand, it would help if some of the players would just think before speaking."
"There is quite a crowd here: several people around this terminal: hence no privacy. I see no signs of editing, but no private communication is possible"
"Tonight's session is being cut short, because it is Sunday, and there is a debate scheduled for 5.30pm. The debate will address the "Amyloid Cascade Hypothesis, 10 years later", and knowing the participants this is likely to be a mixture of fun and serious jibes at each other. I will report on the carnage tomorrow. Peter logging off."

Peterdavies leaves.

Martha_merton leaves.

20 July 1998. Peterd enters. Msmith enters. Peterd says, "Hi, Peter Davies on line"

Msmith says, "Hi, Peter, Mark Smith from Cleveland here. How's the show so far?"

Peterd says, "Hi Mark, You missed a great debate last night. Bob Terry forced at least a restatement of the "amyloid cascade hypothesis"."

Msmith says, "About bloody time....What's the latest twist on the amyloid theory...surely they didn't admit epiphenomena"

Peterd says, "No, they wouldn't back down that far, but there was general aggreement that aggregation and deposition of beta A4 peptide was NOT the critical event in AD."

Msmith says, "Wow! Impressive comedown. So where are they heading now? I assume aggregation is not the way (poor pharmaceutical companies)."

Peterd says, "Even John Hardy had to admit that it is clearly some alteration in APP processing or trafficking that was likely to be the issue: He said that he never intended to imply that amyloid (which Bob defined as extracellular, fibrillar, congophilic material) was the key element. Now no one has any idea what is the key: there is a lot of talk of intracellular betaA4, but it seems that no one has seen this in AD brain yet, so it remains hypothetical.
Al Roses said that as a pharmaceutical company exectutive, he's seen millions wasted on trying to get at amyloid: when the issue should have been APP and ApoE all along."

Msmith says, "As Jim Joseph like to call "The Church of the Holy Amyloid", I guess it now comes down to believe....we can't see it, measure it, or touch it....but it must be out there....believe us!"
"Related to Roses....surprising that most of work on apoE is actually related to amyloid...processing, 1-40/2...etc."

Peterd says, "Al Roses made similar remarks to Jim. You'll be pleased to hear that the mitotic hypothesis receives important support from Thomas Arendt and from the Mandelkow's...."

Msmith says, ".....Anyone else interested in the mitosis angle?"

Osmand enters.

Peterd says, "No one else that I caught. Aside from that, there is a lot of talk but not much data about the tau mutations. Hi Alex."

Msmith says, "Alex....what is this..only Brits allowed?"

Osmand says, "Hi Peter"

Msmith says, "What do the tau mutants do?"

Peterd says, "Alex qualifies: his accent is almost there."

Msmith says, "Barely!"

Msmith smiles.

Peterd says, "The latest data I can get is that while the tau mutations have so far only been found in frontotemporal dementia, they all (and there are 7 different mutations now) result in massive neuronal death in frontal and temporal cortex."

Msmith says, "Any proposed mechanism....microtubules, PO4?"

Osmand says, "Are ubiquitinylation or apoptosis involved in FTD?"

Peterd says, "I think this is going to be tough to sort out. Everyone talks interference but neither I nor Eva Mandelkow agree that this is likely."

Msmith says, "Ubiq....I think so, Apoptosis....never!"

Rockwood enters.

Peterd says, "Don't know about ubiquitin, I don't think anyone has looked at that yet. Apoptosis will be difficult to see, until animal models are made. The cell death in the FTD cases is all over by the time the patient comes to autopsy."

Osmand says, "Do the tau mutations show 100% penetrance?"

Peterd says, "Julia: good to see some one is in my lab."

Peterd says, "As far as we know, all tau mutations have 100% effectiveness."

Rockwood says, "I'm here pushing back the frontiers of science - I think everyone else is at lunch."

Peterd says, "I guess since I'm here, it may be long lunch, at least for CW."

Rockwood says, "Has there been any additional data presented on the FTD mutations?"

Osmand says, "Have you heard any data about this 'plant extract' that Alan Snow and Proteotech are claiming as a miracle cure?"

Peterd says, "No data at all on the FTD cases has been presented. There have been some reports of additional polymorphisms in PSP: and Rudi Tanzi says this must mean that there is a mutation in tau that has not yet been found."

Peterd says, "I saw Alan Snow, but have not heard about any plant extract that does anything. I will look up when he presents, and see if I can catch the talk."

Msmith says, "Anything new related to oxidative damage, free radicals etc? Also, more to the point, what am I missing as regards beer and nightly entertainment?"

Peterd says, "I think the oxidative stress symposia are still to come: today was tau, amyloid and vascular. This is a hard meeting to keep up with, because there are four sessions of talks running at the same time, and they are quite far apart."

Osmand says, "Did Sisodia have anything new about presenilins?"

Peterd says, "I refuse to answer your question reagrding entertainment on the grounds that I might incriminate myself."

Msmith says, "Sounds pretty good then!"

Peterd says, "Sam and Peter Hyslop both talk about the fact that the PS1 and PS2 proteins seem to exist as parts of a large complex in the cell, but not with APP: with a host of proteins not all defined yet."

Osmand says, "Any agreement on localization of PSs?"

Peterd says, "Funny that the lots of the work on the PS proteins does not emphasize the ER localization. It seems that cleavage of both of the proteins occurs, and that the complex exists in the cytoplasm, as far as I can gather. Curious that this does not seem to be discussed too much any more."

Teplow enters. Wasco enters.

Peterd says, "As I was saying, the amyloid guys lost badly"

Osmand laughs hysterically. Wasco leaves.

Peterd says, "I may lose the keyboard at any moment. Brain Cummings is here to keep me honest: I was only joking about the debate: come back Wilma!"

Teplow leaves.

Msmith says, "What happened.....did the bar open up?"

Peterd says, "There are a very large number of talks here that seem to be implying that there is a tight relationship between cerebrovascular disease and AD. It would seem that the developing opinion is that vascular diesase is (or may be) a major risk factor for AD. This is news to me, and there is a debate on this issue going on now."

Msmith says, "Or perhaps it closed."

Conrad enters. Rockwood leaves.

Peterd says, "The bars never close in Amsterdam"

Conrad says, "Anything new on PSP?"

Msmith says, "Now I am mad that I decided not to go! Who is pushing the vascular idea...Sparks?"

Peterd says, "Just more polymorphisms, Chris."

Msmith says, "It certainly makes sense of the ApoE story also"

Msmith says, "Peter et al. I'm off now....thanks for the chat....I will check in later this week for another update. Cheers!"

Peterd says, "No: everyone is pushing this now: whole sessions devoted to the issue. Larry Sparks is fuming that he told everyone this was true years ago, and couldn't get it puslished or funded: now everyone is all over this, and cholesterol regulation of APP processing. Cheers Mark!"

Msmith leaves.

Conrad says, "Is the meeting fairly clinical?"

Osmand says, "Seems that we are still being educated by nuns! All the best, Peter, I'll log in later in the week."

Peterd says, "The tau sessions are very much more crowded than I have ever seen before. Braak's talk was given to standing room only, with people pushing and shoving to get in. There is actually very little clinical stuff here, perhaps one session in four. Hundreds of posters each day, probably more than half basic science."

Peterd says, "Bye Alex. Any progress on the sequencing, Chris?"

Conrad says, "A few of the constructs have been sequenced but I have sent them back up to confirm the results. Marisol says hi."

Osmand leaves.

Peterd says, "Glad to see there are a few of you in the lab: Hi Marisol."

Conrad says, "Well, I have to get back to work, my timer is calling, talk to you soon."

Peterd says, "See ya soon Chris" Conrad says, "Julia says so long and she will talk to you, tomorrow."

Peterd leaves. Conrad leaves. Wasco enters. Wasco leaves. Zalie127 enters. Zalie127 leaves. Carolyn enters. Carolyn leaves. Cweihl enters. Cweihl leaves. Chris enters. Chris leaves. Cweihl enters. Cweihl leaves. Keith enters. Keith leaves. Paula enters. Paula leaves. Mjrussell enters. Mjrussell leaves. Mjrussell enters. Mjrussell leaves. Mjrussell enters. Mjrussell leaves. Mjrussell enters. Mjrussell leaves. Mjrussell enters. Mjrussell leaves. Abetaman enters. Adnerdboy enters. Abetaman leaves. Adnerdboy says, "this is cool!" Adnerdboy leaves. Dsyang enters. Dsyang leaves. Dsyang enters. Dsyang leaves. Dsyang enters. Dsyang leaves. Dsyang enters. Dsyang leaves. Dsyang enters. Dsyang leaves. Terauchi enters. Terauchi leaves. Jamesv enters. Jamesv leaves. Jamesv enters. Jamesv leaves. Montezuma enters. Montezuma leaves. B_hyman enters. B_hyman leaves. Marthaluke enters. Marthaluke leaves. Marthaluke enters. Marthaluke leaves. Marthaluke enters. Marthaluke leaves. Jamesv enters. Jpalac enters. Jamesv leaves. Jpalac leaves. [APPEARS AS THOUGH WE HAD CASE OF TIME ZONE CONFUSION...]

21 July 1998. Rockwood enters. Peter enters.

Peter says, "Hi Julia."

Rockwood leaves. Peter leaves. Peter enters. Peter snores loudly. Peter falls fast asleep.

Peter says, "This morning I attended the amyloid session, devoted to the development of therapeutics aimed at reducing beta1-40 and or 1-42 concentrations. Most of the presentations were very vague and gave details of the strategies being used, but without specific results. The exception was Barbara Cordell, who presented some very interesting data on the nature of the gamma secretase activity, teased out by using a very well designed set of APP deletion and point muations. Barbara suggested that the gamma secretase may involve two distinct activities, a secretase cleaving at residue 46 (in the beta peptide numbering), and a carboxypeptidase chewing away the end, down to either 42, 40, or 39 amino acids long. The specificity of the secreatase activity does not seem to be too tight, and this may in fact be one activity amoung several other proteases. This question cannot yet be settled, and all of the attempts to define inhibitors of secretase activities, whether beta or gamma, suffer severely from the failure to purify or even identify these enzymes."

Peter says, "This afternoon I was at the Lewy Body session, an "add-on" symposium which took up our free afternoon. Several speakers stressed the advantages of using antibodies to alpha-synuclin in the pathologic diagnosis of DLB, and John Hardy (Mayo Clinic, Jacksonville) reported new data on a large pedigree with what is probably DLB. John has found a candidate region on chromosome 4, distinct from previously reported regions, that appears to house the gene defect in this family."

Zalie127 enters.

Peter says, "Hi Zalie127"

Zalie127 leaves.

Adranovs enters. Adranovs leaves. Zalie enters. Zalie leaves. Sissy enters. Sissy leaves. B_hyman enters. Osmand enters. B_hyman leaves. Osmand leaves. Msmith enters. Msmith leaves. Hendricj enters. Hendricj leaves. Mirizarry enters. Mirizarry leaves. Peterdavies enters.

Peterdavies says, "Hello, this is not really Peter Davies, but an imposter."

Peterdavies throws its head back, cackling with glee.

Peterdavies says, "Anyone there? I should have sent a reminder notice out yesterday.... Things have been CRAZY."

Peterdavies attempts to calm itself. Marthakigal enters.

Peterdavies says, "Hello Martha."

Marthakigal says, "Hallo peter."

Peterdavies says, "This is the real thing: the real Peter took over from an imposter!"

Marthakigal says, "Glad to hear it!"

Peterdavies says, "This was the first good day at the meeting: some really good science was presented."

Marthakigal says, "In that case, almost a pity it's over soon."

Peterdavies says, "Personally I can't wait until this is over"

Marthakigal says, "This is also general opinion in the lab."

Peterdavies says, "Tomorrow I leave for England, and will not be on the web tomorrow."

Marthakigal says, "Synchronisation probs. I understand your last comment."

Peterdavies says, "This is still an insecure link."

Marthakigal says, "I presumed so."

Peterdavies says, "Brian Cummings will take over from me for tomorrow, and I will be back on line on Monday evening, all being well."

Marthakigal says, "Back at keyboard. My research continues. Online Publication imminent."

Peterdavies says, "I haven't seen any reprints or copies of the journal as yet. Are these expected soon?"

Marthakigal says, "They may be there already. I got some today. Someone else yesterday."

Peterdavies says, "Does everything look the way it should?"

Marthakigal says, "As far as I can tell. Only one paper may be problematic. Not yours though. They seem ok."

Peterdavies says, "Good to hear: a job well done!"

Marthakigal says, "I have Dr. Merton here. He will leave a message for you elsewhere. Hey! Thanks!"

Peterdavies says, "Thank you: I have been in regular contact, which has been very helpful in certain efforts."

Peterdavies says, "The meeting ends tomorrow, but I will not attend any further scientific sessions. Today I learned a lot"

Marthakigal says, "Yes. He has been calling here a lot unexpectedly and his support was and is most helpful. I think we should discuss this in more depth ASAP. My connection is not so good. I think I have to leave before it crashes."

Peterdavies says, "Next Monday will the the earliest chance: but Tuesday will be the first full day at work" Marthakigal says, "Enjoy your trip. Looking forward to Monday or whenever. Martha."

Marthakigal leaves. Peterdavies falls fast asleep. Peterdavies snores loudly. Peterdavies squirms. Peterdavies snores loudly. Peterdavies sneezes. Peterdavies snarls angrily. Peterdavies smirks. Peterdavies smiles. Peterdavies falls fast asleep. Peterdavies leaves.