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The biology of Alzheimer’s – and how we might find a cure
How does Alzheimer's disease work?
Lou Reese is a co-founder and a member of United Neuroscience's Board of Directors. He currently serves as C_O of United Neuroscience. Lou co-founded an investment and advisory firm with active investments in real estate, energy, hospitality, and life sciences. His investments focus on achieving global impact in critical important areas through innovative models and approaches. He received his B.A. from the University of Pennsylvania and attended Columbia Business School.
LOU REESE: Why do people get Alzheimer’s? How do you differentiate amongst the different types, and what’s really going on?
With imaging now we can see the accumulation of certain toxic proteins in people’s brains. There is general consensus that there are a number of these that are implicated in the disease. A-beta (or Beta-Amyloid), tau, alpha synuclein, and others. I would say those are the three primary culprits.
Now there are people that argue that it’s all microbiome based, and there are people that argue that it’s 100 percent diet and exercise-based, unrelated to the microbiome. And there are people that have a whole variety of approaches to this, none of which I believe are accredited or discredited in a conclusive way.
That’s one of the main reasons why I focus on this ecosystem and this village that it takes to solve these problems. I don’t think this is a silver bullet disease. I think this is a finding out and unveiling and uncovering the different pieces that define it.
And just very recently we couldn’t image for A-beta or beta amyloid, so there was no way to know that. Very recently we couldn’t – there are new serum based biomarkers that are coming along to measure tau levels that are really, really interesting. All of this gives us insight into the accumulation and the timing of the accumulation of these toxic proteins.
So I don’t know, the one, two, three biological assessment, this is the analogy that I always use: Imagine you go into a sports bar and there’s a little guy with glasses and he walks up to the biggest guy in that place and the guy is just all steroided up and he’s got veins popping out of his neck. And he walks up to the guy (and he doesn’t know him) and he just pokes him right in the chest. There’s going to be a cascade of events caused by that poke. Maybe he’ll get his jaw broken. Maybe he’ll have some ribs cracked. Maybe he’ll be thrown out of a window. Maybe the cops will come. Maybe they’ll have to write up a police report. Maybe they’ll have to go to a court case after that. All these things could happen. Now depending on where you saw that fight, what started it? You would have no idea. And all of your assessments, all your assumptions would be wrong if you didn’t see that guy unprovoked poke that person in the chest. So where is the poke with Alzheimer’s? There’s a lot of debate around that. But where that cascade of events occurs there’s becoming more clarity around that. So I hope that’s helpful. If you look a it from a disease progression state these toxic proteins are building up in your brain 10, 15, 20 years before you have any symptoms.
So this is something that is laying there in a lot of us and just waiting for its chance to jump up. And so knowing that and having seen that in lots and lots of people—there’s a lot of studies that walk through this but the general thought is that you have the beta amyloid levels rising. Thereafter you have the tau levels rising. Thereafter, and consequence and in concert with the tau level rising there’s some correlation with the actual cognitive impairment. Now that doesn’t mean that that’s the biology of Alzheimer’s conclusively. That means that this is an evolving story and this ties back into this village and ecosystem.
The reason I’m so excited is because we actually have answers to some of these questions now. So at least we know that these are toxic or mis-folded or in some way non-advantageous proteins. So we’re starting to understand that and being able to see it and track its growth, intervene earlier. All of those things are really compelling.
So the goal is to create endobodies naturally that cross the blood brain barrier and engage the toxic forms of A-beta plaque. And the way that I think about it is like this: A-beta is naturally occurring in everyone. Beta amyloid is made by every person’s body. It’s when it starts to get stuck together that it becomes a problem.
So first two of them get stuck together, it’s a dimer. Then a bunch of them get stuck together, it’s an oligomer. Then a bunch of those get stuck together, it’s a fibril. Then a bunch of those get stuck together, it’s a plaque.
So by the time it gets to be a plaque it’s a toxic form of that protein. So what I’m excited about is that I believe that we can target, safely and effectively, the toxic forms of that misaggregated protein, that aggregated protein, and remove them—safely!
We turn on the body’s ability to generate endobodies. The endobodies that we generate with our lead compound are against the A-beta targets. And so why are we doing that at UNS, United Neuroscience? At United Neuroscience we’re activating the body’s immune system to target toxic proteins. In the case of our lead compound it’s against beta amyloid.
What happens is that the body identifies these toxic forms, only the toxic forms so it’s highly specific, or primarily the toxic forms and binds to them in the brain and removes them.
My audacious goal for my team is: if you can go early enough and your product is safe enough there’s absolutely opportunities to prevent the accumulation of these proteins in the very first place—so before there are symptoms, before there are any of those things.
We vaccinate 500 million pigs a year for less than a dollar a dose with over 70 percent margins. If you think about – now obviously humans there’s slightly different CMC and different manufacturing, but the bottom line is that technology platform is going to be accessible, and it’s going to be available for every one of the millions of people that are suffering from this disease. And it’s going to be able to solve these problems potentially in ways that we envision to be, or be a part of a solution for these problems, in ways that we really envision to be beneficial for society, for people and for their families and for this global impact idea.
What could be a better way to wake up and spend your time than really being able to change people’s lives and make them better? So that’s kind of the biology wrapped in a nut, you know.
- Alzheimer's kills about 83,000 people a year and over 5 million people are afflicted with it.
- Lou Reese, the co-founder of start-up United Neuroscience, thinks that there's a cure on the horizon.
- Could it be prevented with a simple vaccine?
Join The Daily Show comedian Jordan Klepper and elite improviser Bob Kulhan live at 1 pm ET on Tuesday, July 14!
Gender and sexual minority populations are experiencing rising anxiety and depression rates during the pandemic.
- Anxiety and depression rates are spiking in the LGBTQ+ community, and especially in individuals who hadn't struggled with those issues in the past.
- Overall, depression increased by an average PHQ-9 score of 1.21 and anxiety increased by an average GAD-7 score of 3.11.
- The researchers recommended that health care providers check in with LGBTQ+ patients about stress and screen for mood and anxiety disorders—even among those with no prior history of anxiety or depression.
Study findings<p>For the study, <a href="https://link.springer.com/article/10.1007/s11606-020-05970-4" target="_blank">published in the Journal of General Internal Medicine</a><em>, </em>Flentje and her team evaluated survey responses from nearly 2,300 individuals who identified as being in the lesbian, gay, bisexual, transgender, and queer (LGBTQ+) community. Most of the participants were white, while nearly 19 percent identified as a racial or ethnic minority. Multiple genders were represented with cisgender women (27.2 percent) and men (24.6 percent) making up a majority of the participants. Sixty-three percent had been assigned female at birth. For the most part, participants identified their sexual orientations as queer (40.3 percent), gay (36.5 percent), and bisexual (30.3 percent).</p><p>The JGIM study participants were recruited from the 18,000-participant <a href="https://pridestudy.org/" target="_blank">PRIDE Study</a> (Population Research in Identity and Disparities for Equality), which is the first large-scale, long-term national study focusing on American adults who identify as LGBTQ+. It conducts annual questionnaires to understand factors related to health and disease in this population. </p><p>Participants filled out an annual questionnaire (starting in June 2019) and a COVID-19 impact survey this past spring. Flentje noted that on an individual level, some people may not have experienced a big change in anxiety or depression levels, but for others there was. Overall, depression increased by a <a href="https://patient.info/doctor/patient-health-questionnaire-phq-9" target="_blank">PHQ-9 score</a> of 1.21, putting it at 8.31 on average. Anxiety went up by a <a href="https://www.mdcalc.com/gad-7-general-anxiety-disorder-7" target="_blank">GAD-7</a> score of 3.11 to an average of 8.89. Interestingly, the average PHQ-9 scores for those who screened positive for depression at the first 2019 survey decreased by 1.08. Those who screened negative for depression saw their PHQ-9 scores increase by 2.17 on average. As for anxiety, researchers detected no GAD-7 change among the study participants who screened positive for anxiety in the first survey, but did see an overall increase of 3.93 among those who had initially been evaluated as negative for the disorder. </p>
Risks among gender and sexual minorities<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="fc3fd1ae68b77bbbf58a6995638d6d65"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/EnUqDjCqg0A?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>The LGBTQ+ community is a vulnerable population to mental health concerns because of their fear of stigmatization and previous discriminatory experiences.</p> <p>Previous research by the Human Rights Campaign has found "that LGBTQ Americans are more likely than the <a href="https://medicalxpress.com/tags/general+population/" target="_blank">general population</a> to live in poverty and lack access to adequate medical care, paid <a href="https://medicalxpress.com/tags/medical+leave/" target="_blank">medical leave</a>, and basic necessities during the pandemic," said researcher Tari Hanneman, director of the health and aging program at the campaign.</p> <p>"Therefore, it is not surprising to see this increase in anxiety and depression among this population," Hanneman said in the release. "This study highlights the need for <a href="https://medicalxpress.com/tags/health+care+professionals/" target="_blank">health care professionals</a> to support, affirm and provide <a href="https://medicalxpress.com/tags/critical+care/" target="_blank">critical care</a> for the LGBTQ community to manage and maintain their mental health, as well as their physical health, during this pandemic."</p>
What should health care providers do?<p>The authors of the study recommend that health care providers check in with LGBTQ+ patients about stress and screen for mood and anxiety disorders in members of that community—even among those with no prior history of anxiety or depression.</p><p>As cases of COVID-19 continue to mount, the sustained social distancing, potential isolation, economic precariousness, and personal illness, grief, and loss are bound to have increased and varied impacts on mental health. Effective treatments may include individual therapy and medications as well as more large-scale coronavirus support programs like peer-led groups and mindfulness practices. </p><p>"It will be important to find out what happens over time and to identify who is most at risk, so we can be sure to roll out public health interventions to support the mental health of our communities in the best and most effective ways," said Flentje.</p>
What we know about black holes is both fascinating and scary.
- When it comes to black holes, science simultaneously knows so much and so little, which is why they are so fascinating. Focusing on what we do know, this group of astronomers, educators, and physicists share some of the most incredible facts about the powerful and mysterious objects.
- A black hole is so massive that light (and anything else it swallows) can't escape, says Bill Nye. You can't see a black hole, theoretical physicists Michio Kaku and Christophe Galfard explain, because it is too dark. What you can see, however, is the distortion of light around it caused by its extreme gravity.
- Explaining one unsettling concept from astrophysics called spaghettification, astronomer Michelle Thaller says that "If you got close to a black hole there would be tides over your body that small that would rip you apart into basically a strand of spaghetti that would fall down the black hole."
The team caught a glimpse of a process that takes 18,000,000,000,000,000,000,000 years.
- In Italy, a team of scientists is using a highly sophisticated detector to hunt for dark matter.
- The team observed an ultra-rare particle interaction that reveals the half-life of a xenon-124 atom to be 18 sextillion years.
- The half-life of a process is how long it takes for half of the radioactive nuclei present in a sample to decay.
A new study looks at what would happen to human language on a long journey to other star systems.
- A new study proposes that language could change dramatically on long space voyages.
- Spacefaring people might lose the ability to understand the people of Earth.
- This scenario is of particular concern for potential "generation ships".