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A study shows that rising levels of brain protein Aß42, not the reduction of amyloid plaques, better explains the cognitive benefits of new Alzheimer’s drugs. This finding challenges the traditional focus on plaques in Alzheimer’s treatment.
A new study reveals that the rise in protein levels due to new Alzheimer’s drugs may explain the slowing of cognitive decline just as effectively as the reduction of amyloid plaques.
In a study that questions the effectiveness of newly approved monoclonal antibodies in reducing cognitive decline in Alzheimer’s patients by clearing amyloid, researchers from the University of Cincinnati discovered that an unintended rise in a critical brain protein’s levels correlates just as strongly with cognitive benefits.
Led by UC’s Alberto Espay, MD, the research was published in the journal Brain.
Study background
For decades, the prevailing theory in the field has stated that a protein made up of 42 amino acids called amyloid-beta 42 (Aß42) hardens into clumps called amyloid plaques, and those plaques damage the brain, causing Alzheimer’s disease.
Espay and team have hypothesized that normal, soluble Aß42 in the brain is crucial for neuron health and that the loss of Aß42, rather than the buildup of plaques, drives Alzheimer’s. This includes published research that suggests dementia occurs not when plaque levels are high but when Aß42 levels drop very low.
According to Espay’s research, the transformation of Aß42 into plaques appears to be the brain’s normal response to biological, metabolic, or infectious stress.
Alberto Espay
Alberto Espay, MD, MSc, professor of neurology at the UC College of Medicine and Director and Endowed Chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders. Credit: Colleen Kelley/UC Brand + Creative
“Most of us will accrue amyloid plaques in our brains as we age, and yet very few of us with plaques go on to develop dementia,” said Espay, professor of neurology in the UC College of Medicine and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute. “Yet the plaques remain the center of our attention in biomarker development and therapeutic strategies.”
Study details
Recently, several new monoclonal antibody medications designed to remove amyloid from the brain were approved after showing they lessened cognitive decline in clinical trials.
Espay and his colleagues noticed that these drugs unintentionally increased levels of Aß42.
“Amyloid plaques don’t cause Alzheimer’s, but if the brain makes too much of it while defending against infections, toxins, or biological changes, it can’t produce enough Aß42, causing its levels to drop below a critical threshold,” Espay explained. “That’s when dementia symptoms emerge.”
The team analyzed data from nearly 26,000 patients enrolled in 24 randomized clinical trials of these new antibody treatments, assessing cognitive impairment and differences in levels of Aß42 before and after treatment. They found that higher levels of Aß42 after treatment were independently associated with slower cognitive impairment and clinical decline.
“All stories have two sides — even the one we have told ourselves about how anti-amyloid treatments work: by lowering amyloid,” Espay said. “In fact, they also raise the levels of Aß42. Even if this is unintended, it is why there may be a benefit. Our study shows that we can predict changes in cognitive outcomes in anti-amyloid trials at least as well by the increases in Aß42 as by the decreases in amyloid.”
Espay said these findings fit well into his larger hypothesis about the root cause of Alzheimer’s, as increasing levels of Aß42 appear to improve cognition.
“If the problem with Alzheimer’s is the loss of the normal protein, then increasing it should be beneficial, and this study showed that it is,” he said. “The story makes sense: Increasing Aß42 levels to within the normal range is desirable.”
However, Espay believes these results also present a conundrum for clinicians because removing amyloid from the brain is toxic and may cause the brain to shrink faster after antibody treatment.
“Do we give patients an anti-protein treatment to increase their protein levels? I think the end, increasing Aß42, doesn’t justify the means, decreasing amyloid,” Espay said. Therapies that directly increase Aß42 levels without targeting amyloid are a focus of research for Espay and his group
We’re rich!
Why post this garbage twice?
Hmmm. Interesting.
Clawing its way up slowly. Breakout at .10. Wonder who’s buying?
Could the absence of information for current shareholders be due to a “quiet period” regarding the spinoff?
I’m referring to the supposed IPO for Zena.
Lack of news is very concerning. Somebody needs to call.
We’d better get shares. I bought Epaz because of the drone business. If we don’t, I smell law suit.
I agree, but shouldn’t that have been on that F-1 that recently came out? Too long for me to wade through🥴.
I saw a story on a Portland, OR tv station this am about a Salem (Oregon) area school planning to try out a detection system made by Evolve, an east coast company that seems to be doing very well and likely eating DTII's lunch. The boys down in Del Mar better get off the beach and get their butts in gear. I was down in Del Mar 2 weeks ago. Should have done a drive by to see if anyone was at work. Unlikely, as it was a beautiful day down there.
Correction:102 mil shares.
Anyone calculate the offering price if the 192 mil shares sell? Looks like 6.8 cents each, with a lockout period of 180 days. Anyone correct me if I hav calculated incorrectly.
With you on all that!
Their administrative offices seem to be top heavy. Why have a Chicago office when PHX is just as easy to communicate with? I think once a military contract comes in there will be more civilian interest. Companies don't want to invest in a product that may suddenly lose support. Neither does the military, but the military has their budget backing it up.
Yes, cash on hand could be scary..
How did you cone up with the 03/21 date?
I have always assumed that the selling of shares was in order to pay salaries and keep the lights on.
Tie in with Amazon seems most logical. This drone has the lifting capacity and the range to meet their urgent and high priority delivery needs.
Yes. Under water till it hits a penny. About 609k shares.
Well spoken Kevin.
I’m holding my nose with my investment here. Hoping for a bit of a profit before wiping this dog shit off my shoes.
How about revealing your source?? Drones are already in widespread use, so highly unlikely to happen.
It seems it would be important for anyone passing through a security system that radiates on a daily basis. I would not like a child of mine passing through even low level radiation every day at school, when 20 or 30 years later they might be diagnosed with a blood cancer like leukemia. Or even for adults like those who work in a courthouse who have to enter on a daily basis. I do also wonder if this system will detect an all plastic ghost gun?
I have not researched it, but does anyone know if there are other non-radiating systems on the market?
Tax loss selling kicking in.
Thanks. I got burned on SNPX, so gonna wait this one out.
How long is this study?
So the drone can lift 80 lbs and stay up an hour; have they ever said the max altitude it can fly at?
Thanks for the info.
I emailed the company 2 days ago; got no response. Anyone on this board live in Austin who could go knock on their door? I'll try phoning tomorrow.
Mystery is what news is about to drop…
When clicking on "newer" or "older", you should not have to scroll up or down to find the next new or old. The beta will greatly slow the scrolling process.. The old version did not always allow this, but this is far worse.
"IQST is a pioneer. Pioneers end up with arrows in their back sometimes, but most of them at least see Wyoming and Montana before the rest of us on their way to Oregon. And plenty of them make it to Oregon."
Interesting you mention Oregon. I live in the incorporated community of Hillsboro to the west of PDX. Take a drive west on Evergreen and the number of huge tech industries under construction or already open will blow your mind. We have lots of water and power to feed these industries.
Too bad the simufilam arm only slowed the decline. Would have at least liked to see it stabilize decline. At lease they did better than the placebo patients.
Interesting finding re neuron synapse repair:
Scientists discover mushroom capable of magnifying memory, boosting nerve growth: Study
New Delhi, IndiaEdited By: Kirtika KatiraUpdated: Feb 11, 2023, 02:02 PM IST
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Edible Lion’s Mane mushroom can help promote neurogenesis & enhance memory, according to a new study. Photograph:(Instagram)
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STORY HIGHLIGHTS
The University of Queensland’s pre-clinical test has found that edible Lion's Mane mushrooms have a significant impact on the growth of human brain cells.
Australian scientists have identified a new active compound in an edible mushroom, Hericium erinaceus, that is capable of boosting nerve growth and even enhancing memory. The University of Queensland’s pre-clinical test has found that edible Lion's Mane mushrooms have a significant impact on the growth of human brain cells.
Researchers feel this discovery could be used to protect against and treat Alzheimer's disease
According to Professor Frederic Meunier from the Queensland Brain Institute, his team has identified new active compounds in the mushroom that improve brain cell growth. "Extracts from these so-called ‘lion’s mane’ mushrooms have been used in traditional medicine in Asian countries for centuries, but we wanted to scientifically determine their potential effect on brain cells," Professor Meunier shared.
"Pre-clinical testing found the lion’s mane mushroom had a significant impact on the growth of brain cells and improving memory. Laboratory tests measured the neurotrophic effects of compounds isolated from Hericium erinaceus on cultured brain cells, and surprisingly we found that the active compounds promote neuron projections, extending and connecting to other neurons," Professor Meunier added.
"Using super-resolution microscopy, we found the mushroom extract and its active components largely increase the size of growth cones, which are particularly important for brain cells to sense their environment and establish new connections with other neurons in the brain," he concluded.
UQ’s Dr Ramon Martinez-Marmol, who is a co-author of the study, feel that the discovery had applications that could treat and protect patients against neurodegenerative cognitive disorders such as Alzheimer’s disease.
"Our idea was to identify bioactive compounds from natural sources that could reach the brain and regulate the growth of neurons, resulting in improved memory formation," Dr Martinez-Marmol said.
Dr Dae Hee Lee from CNGBio Co, which has supported the research project, said that the properties of lion’s mane mushrooms had been used to treat ailments and maintain health in traditional Chinese medicine since antiquity.
"This important research is unravelling the molecular mechanism of lion’s mane mushroom compounds and their effects on brain function, particularly memory," Dr Lee revealed.
I’n currently in the OC, CA right now. Seems every kid under 16 has an e-bike. I’ve seen them doing wheelies on uphill streets. The cops have posted electric signs warning that traffic laws will be enforced. Place is full of rich kids.
Thanks coach.
Is there any valid science to this, or is Lane Simonian way out of his league:
The treatment of Moderate Alzheimer's disease requires intervention after the over-activation of NMDA receptors.
BioVie does this by reducing the phosphorlyation of ERK (Extracellular Regulatory Kinase) and by inhibiting NF-kB (Nuclear Factor-kappa Beta).
Panax ginseng does this by inhibiting the activation of p38 MAPK (Mitogen-Activated Protein Kinase) and NF-kB (Nuclear Factor-kappa Beta).
Panax ginseng also contains components that scavenge and partially reverse the damage that oxidants such as hydrogen peroxide and peroxynitrite do to the brain.
It remains to be seen if BioVie's inhibition of the phosphorylation of ERK and its inhibition of NFk-B is enough to substantially alter the course of Alzheimer's disease.
January 18, 2023
AiAdvertising Releases Preliminary Unaudited Q4 Financial Results in Conjunction with Shareholder Update Letter
2022 Revenue Increases to $7.1 Million on New Customer Agreements and SaaS Platform Solution
Q4 Revenue of $2.4 million Increases 33% Sequentially from $1.8 million in Q3 Platform License Revenues Increased 561% from Q1 to Q4 2022 Company Anticipates Reaching Cash Flow Break in Q1 2023
SAN ANTONIO--(BUSINESS WIRE)-- AiAdvertising, Inc. (OTC: AIAD), a next-generation AdTech company focused on harnessing the power of artificial intelligence (AI) and machine learning (ML) to build software for today’s marketing leaders, has released a letter to its shareholders from CEO Jerry Hug including preliminary select financial results for the year ended December 31, 2022.
Dear Fellow Shareholders,
2022 was a pivotal year for AiAdvertising and for our business, punctuated by the transition from operating as an agency with inconsistent and unpredictable revenue to a SaaS platform solution with scalable and predictable, monthly recurring revenue. Driving our performance is our proprietary software the Campaign Performance Platform (CPP), the industry’s first cloud-hosted ad management solution that leverages AI and connects marketing investments to sales revenue. Over the past 12 months, we have cemented our status as one of the most innovative, efficient, and advanced solutions and as a clear market leader in the rapidly emerging AI-as-a-Service (AIaaS) in the AdTech category.
Our CPP is giving marketers the ability to leverage intelligent automation to make predictions at scale, bridging the gap between CRM and AdTech. CPP uses AI to reduce what would typically take 24,000 man hours into 36 hours of marketer plus machine hours. The CPP includes services such as: organization of disparate CRM and customer data, automation of persona development, predict and render dynamic creative assets, look-a-like audience curation, omni-channel activation, and real-time performance management. CPP first helps to prioritize client goals and objectives and connects, organizes, and cleans customer data, transformed into actionable insights. Its AI dynamically identifies behavioral insights in days, not months at a fraction of the cost of traditional methods.
We began 2022 with early signs that advertisers were embracing our AIaaS platform solution, signing nine new platform license agreements at the beginning of the year which totaled more than $5 million in annualized revenue. An additional strategic relationship and licensing agreement with Campaign Nucleus validated what we believe to be a game- changing technology in the $21 billion marketing and advertising category. As the year progressed, we added two more Caterpillar dealers, bringing our total to 4 of the 39 independent dealers across the US and Canada, and added several new clients across various categories. By the end of the third quarter, we had signed a total of 11 platform license agreements since the beginning of the year, totaling more than $0.75 million in annualized revenue.
Our customers quickly began to see momentum with CPP, leveraging AI in the platform to drive their performances. BioHarvest Sciences achieved early success using CPP, with initial positive results of over 180% increase in revenue from their Google spend and a 48% higher Return on Ad Spend (ROAS). AiAdvertising played a critical role in scaling BioHarvest’s platform advertising. As of the third quarter, AiAdvertising had seen further improved results, and BioHarvest’s overall ROAS since April 2022 increased by 90%. We also saw early success in helping drive the expansion stage of the Act! CRM and Marketing Automation Platform. Our program contributed significantly to its lead volume and at a lower cost per lead. This has led directly to thousands of new prospects being introduced to the upgraded Act! product portfolio.
Operationally, 2022 saw numerous changes as our growth accelerated. I was privileged to be appointed CEO and given the opportunity to lead AiAdvertising into its next exciting phase. We underwent a comprehensive rebrand with a focus on our AI-Driven Campaign Performance Platform. This included a new corporate image and identity reflective of our forward-thinking approach to advertising technology, while challenging the status quo. This also included a new corporate website and next generation investor relations website. To complement our ongoing efforts to enhance communications with the investment community, we engaged MZ Group to lead our strategic investor relations and shareholder communications program.
Taken together, our focus on new customers and our SaaS platform solution culminated in preliminary, unaudited 2022 revenue of $7.0 million, a 3% improvement from the prior year, and a significant sequential increase of 33% from $1.8 million in the third quarter to $2.4 million in the fourth quarter of 2022. However, Platform License (SaaS) revenues increased 561% from the first to fourth quarters of 2022 and the contribution to revenue increased over 200% to 12% as our CPP platform continues to gain significant traction, including a 48% increase from the third to fourth quarters. Perhaps more importantly, we believe we will achieve cash flow break even from operations in the first quarter of 2023.
Looking ahead, we are excited by the initial results of our customers’ success using CPP and believe we are well-positioned to grow the value of our technology and customer base in a wide range of industries including finance, specialty retail, hospitality and leisure and industrial. We will continue to scale our platform with direct-to-consumer brands that are looking to deploy large budgets at scale without having to add headcount. We remain highly focused on executing on our sales roadmap to grow recurring revenues and driving gross profit margin. Thank you to all our shareholders, partners, and staff for your support on our journey. I look forward to another exceptional year at AiAdvertising.
Sincerely,
Jerry Hug
Chief Executive Officer
About AiAdvertising
AiAdvertising, Inc. (OTC: AIAD) is a next-generation AdTech company that is harnessing the power of artificial intelligence (AI) and machine learning (ML) to build software for today’s marketing leaders. We are focused on eliminating waste and maximizing the return on digital ad spend.
Our flagship product, the Campaign Performance Platform, is a subscription-based, end-to- end Ad Management solution. The platform empowers brands and agencies to easily target, predict, create, scale, and measure hyper-personalized campaigns.
For more information about the Company, please visit www.AiAdvertising.com or our LinkedIn or Twitter pages.
Forward-Looking Statements
This press release may contain “forward-looking statements.” Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements are included in our filings with the Securities and Exchange Commission, including the “Risk Factors” section of our annual report on Form 10-K for the year ended December 31, 2020. Any forward-looking statement made by us in this release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, except as may be required under applicable law.
View source version on businesswire.com:
https://www.businesswire.com/news/home/20230118005287/en/
Investor Contact:
Larry Holub/Chris Tyson 312-261-6412 AIAD@mzgroup.us www.mzgroup.us
Source: AiAdvertising, Inc.
Volta, an EV recharging co, bought today by Shell, all cash, for a modest premium over current SP.