Online Alzheimer's Afternoons Seminar Series

[Fiver]

For those interested in the nuts and bolts details of AD research I wanted to let you know of a Alzheimer's Afternoons Seminar Series that is occurring online during the COVID-19 shut down. It is focused on apoe.

It is run by a group of researchers as a lab seminar series, organized via Twitter by ApoE Discoveries @ApoEdscvr.

This is a group of early to mid-career researchers. Not the famous names but the "in the trenches" AD researchers focusing on apoe4, and building their scientific careers.

It has an informal style. But good quality research.

Seminars are held online via Zoom at 3:00pm ET on Tuesdays and Thursdays. Listeners will see the presenter and slides, but not other listeners. Some Q&A occurs via a text-based chat function.

Seminars are recorded, and you can listen anytime.

You can see the speakers and topics listed here:

The first seminar had 160 "listeners".

This Twitter group also collated posters from an online Alzheimer’s Research UK conference, which was cancelled due to the pandemic. You can see these on Twitter.

[slacker]

Seminars are recorded, and you can listen anytime.

Thanks Fiver. It wasn't clear to me how to listen to past recorded talks (ie Lance Johnson from UK - go wildcats!). What am I missing?

[Fiver]

I haven't tried that yet but I think the directions are buried in those tweets. There has been only one recorded so far. I'll look into it and report back....

[AKA]

Seminars are recorded, and you can listen anytime.

Thanks Fiver. It wasn't clear to me how to listen to past recorded talks (ie Lance Johnson from UK - go wildcats!). What am I missing?

Slacker, I saw this note just below the zoom link: " * presentations will be recorded and posted online for 12 hr to accommodate other time zones (unless requested otherwise by the speaker)" ............ I didn't see a link to get to the recording.

aka

[slacker]

" * presentations will be recorded and posted online for 12 hr to accommodate other time zones (unless requested otherwise by the speaker)"

Thanks AKA; good eyes! Not quite anytime.

[Fiver]

Oh no. Sorry, I misread that.

I took notes and plan to post summaries here, if that helps.

[aphorist]

I took notes and plan to post summaries here, if that helps.

If you can post yesterday's summar, I'd be interested. I just saw this link you provided and yesterday's topic looks interesting. Today, not so much.

[slacker]

I took notes and plan to post summaries here, if that helps.

That would be fantastic. Thanks in advance. It's wonderful that these talks are open to the public, even if for a limited time.

[Fiver]

Some notes from the first two seminars:

Seminar #1. March 26. Lance Johnson (U. Kentucky). Tipping the energy balance: APOE, AD and cerebral metabolism. Dr. Johnson started by explaining the theory that apoe4 carriers use "fuels" differently. Specifically, that apoe4 astrocytes and microglia - which tend to neurons - are less able to process sugars by the usual process of glycoloysis + TCA cycle. Instead, hypothesized that they do glycolysis to lactate which provides less energy and requires another cell or tissue to recycle lactate later. The theory also predicts that apoe4's would do more beta-oxidation of fatty acids to make up for this. This process is slower, produced more toxic reactive oxygen species, and can actually end up using the protective myelin sheaths of neurons as fuel. (This is a theory being investigated by many others) Then, he noted the Dr. Alzhemier observed "lipid droplets" in the brain of patients in 1907. They wondered if apoe4s accumulated more lipid droplets. They found that apoe4s make more droplets, but they are smaller. This might be explained in part with lower activity of ABC proteins, which facilitate lipid efflux from cells. The higher number of small lipid droplets in apoe4s got worse with age. In another set of experiments they feed apoe4 cells fats labeled with radioactive carbon and found that apoe4 cells were doing more beta-oxidation (or burning) of these fats. Then they conducted interesting experiments on 94 human subjects (33 E4s, all <55 years old, healthy), looking at their metabolic activity at rest, with and without consuming sugary drinks. Found that: E2s had high sugar usage and the expected increase in oxygen intake and usage this requires whereas E4s had lower sugar usage and no increase in oxygen intake or usage. There conclusion from this collection of experiments - some of which were recently published - was that the data support the original theory. He compared the metabolism of apoe4 astrocyctes and microglia to the "Warburg effect" seem in cancer tumors, wherein cancerous cells do a lot of glycolysis without the TCA cycle - an ineffecient process - and churn out lactate acid as a waste product. Mentioned the a high fat diet....usually researcher talk from a super size me type fast food diet....made this more pronounced. My take: this jives with lots of other observations that apoe4 cells do a poor job at glycolysis+TCA cycle to use sugars for energy production, instead dong an inefficient glycolysis to lactate process and burning fats.

[Fiver]

Seminar 2. Gareth Howell. The Jackson Lab. MODEL-AD: Towards the next generation of mouse models for Alzheimer's disease. The general idea was that progress in AD has been slowed by poor mouse models. They participate in the MODEL-AD group, hundreds of researchers, working to create and test better mouse models. Started by describing new mouse models with human apoe4/4. Noting that they see a break down in brain vessels, specifically fibrin leakage into the brain, but only in mid-life mice.....not in younger apoe4 mice. In this mice the flow of blood was reduce, as visualized by PET scans. Currently exploring the potential benefits of exercise to correct this in 4/4 vs 3/3/ mice. Find that 4/4 mice as just as good at exercise and had no observed differences when young. Found that "mouse exercise" (my term) helped prevent the problems the 4/4 mice normally had when older....but only if exercise was started when mice were young. In general, he noted that neither human 4/4/ genes nor age are sufficient to cause AD in these mice. Some other trigger seems to be needed. They also developed mice with human trem2 and made combinations of mouse populations with apoe genotypes and/or trem2 genotypes. Measured "frailty" in all these populations and noted no differences. Also noted that apoe4 protein levels don't seem to change with age in these mice. Noted that amyloid beta accumulation seems to be a trigger to cause problems - but the results were inconsistent. My take: It's a really impress - and huge - group collaborating to generate better tools for future experiments. It seemed to me that their data support the idea that apoe4s tend to have a more fragile brain system, especially when older.