![](//www.4rfv.com/4rfv_news_images/scripps_scripts/S6JMKCJR1LFT_0.jpg)
Scripps Research scientists uncover new molecular drivers of Alzheimer's By recording detailed electrical and protein measurements of individual brain cells, researchers revealed new potential drug targets for the neurodegenerative disease.
May 22, 2024
LA JOLLA, CA According to the US Centers for Disease Control and Prevention, at least 5.8 million Americans are currently living with Alzheimer's disease, which is the most common form of dementia. There is no cure for Alzheimer's, in part because scientists do not yet have a full understanding of what causes the disease. But a new study from Scripps Research is shedding light on the molecular drivers that could contribute to Alzheimer's progression.
In the study, published in Advanced Science on May 21, 2024, the researchers used a new technique for studying single, living brain cells affected by Alzheimer's disease. By measuring the electrical activity of single neurons and the protein levels within those neurons, the scientists discovered new molecules linked to Alzheimer's. The hope is these molecules could be targeted by drugs to treat or slow the progression of the neurodegenerative disease in the future.
Close collaboration among Scripps Research's professors, including clinical neurologist Stuart Lipton, MD, PhD, protein expert John Yates, III, PhD, and bioinformaticist Nicholas Schork, PhD, (who is also the deputy director and distinguished professor of quantitative medicine at The Translational Genomics Research Institute, or TGen) enabled the scientists to develop this biotechnology feat.
It was mind-boggling to me that we could take one cell, measure its electrical activity on the order of one-millionth of one-millionth of an ampere, and then look at thousands of proteins within that same cell to allow us to find the proteins that drive Alzheimer's-related abnormal electrical activity, says senior author Lipton, who is also the Step Family Foundation Endowed Professor and co-director of the Neurodegeneration New Medicines Center at Scripps Research. But the beauty of this method is that it lets us uncover novel targets for Alzheimer's disease and related dementias.
Previous research by Lipton and others has shown that certain neurons become overactive in the brains of people with Alzheimer's, sending electrical signals that are stronger or more frequent than usual. Evidence suggests that this overactivity (also known as hyperexcitability) contributes to the cognitive decline associated with Alzheimer's.
In the new work, Lipton and colleagues developed a system in which scientists can take precise measurements of individual brain cells and then compare those affected by Alzheimer's with healthy cells. Lipton's group, who has previously developed methods for precisely measuring the electrical activity of neurons, teamed up with Yates to use mass spectrometry to identify levels of over 2,250 proteins in each nerve cell. Mass spectrometry can identify and quantify proteins from cells, but these analyses have traditionally been done on bulk collections of cells. Recent advances are permitting measurements at the single-cell level.
In the new system, known as single cell (sc)Patch-Clamp/Proteomics, a tiny glass tube filled with a salt solution is used as an electrode to measure the electrical activity of a cell, and then extract the cell for protein studies with mass spectrometry.
This approach allows us to connect perturbations of electrical functions to molecular events in neurons, which is an exciting application of proteomics, says Yates.
The scientists analyzed the electrical patterns and protein levels of about 150 neurons and then used computational tools applied by Schork to find associations between hyperexcitability and abnormal protein levels. They pinpointed nearly 50 proteins that were present at higher or lower levels in hyperexcitable Alzheimer's cells compared to healthy cells.
Some of these proteins were already known to be associated with Alzheimer's, but many were not, says Lipton.
The proteins were involved in many diverse functions of neurons, including control of electrons in free radicals (redox modulators), energy metabolism and inflammation. Fifteen of the proteins stood out as having particularly high or low levels in Alzheimer's neurons, and Lipton's group is planning follow-up studies on some of these molecules.
He also plans to expand the use of scPatch-Clamp/Proteomics for drug screens testing whether potential Alzheimer's drugs fix both the hyperexcitability of neurons and the abnormal protein levels. He is correlating these findings with experiments on larger groups of brain cells obtained from patients with Alzheimer's known as cerebral organoids, or mini-brains.
One cell doesn't always tell the whole story, Lipton explains. Some of the dysfunction in Alzheimer's has to do with how cells interact with each other, so if we can repeat this kind of study in a mini-brain organoid, we may make additional discoveries.
Lipton notes this method could be applied to drug discovery efforts for additional brain-related diseases.
This new approach to personalized medicine based upon protein expression and electrical activity of a single Alzheimer's neuron could revolutionize drug discovery not only for this disease but other neurological diseases, which has lagged far behind other therapeutic areas, he adds.
In addition to Lipton and Yates, authors of the study, Single cell patch-clamp/proteomics of human Alzheimer's disease iPSC-derived excitatory neurons vs. isogenic wild-type controls suggests novel causation and therapeutic targets, are Swagata Ghatak, Jolene K. Diedrich, Maria Talantova, Henry Scott, Meetal Sharma and Matthew Albertolle of Scripps Research; and Nivedita Bhadra and N
North America Stories
15/06/2024
What Exactly Is Dad Rock? 21 Songs that Explain the Totally Not Embarrassing Gen...
15/06/2024
MGM Plus has ordered The Institute, a thriller based on a Stephen King novel, for a series. Ben Barnes and Mary-Louise Parker will star, and Jack Bender and Ben...
15/06/2024
With the retirement of Mike McClain as senior VP and general manager of WOFL-WRB...
15/06/2024
Jimmy Fallon, host of The Tonight Show, has renewed his deal with NBCUniversal, extending his tenure through 2028. Fallon began hosting the show in 2014. Before...
15/06/2024
Prime Video has greenlighted three Tom Green projects coming out of the Amazon Connected Worlds event in Toronto. They include an unscripted series, a comedy sp...
15/06/2024
Tegna said it was ending production of Daily Blast Live, which has aired on Tegna stations since it was launched in 2017....
14/06/2024
Program Uplifts Emerging Filmmakers Ages 18 to 25...
14/06/2024
PARK CITY, UTAH JANUARY 21: Actor Jennifer Connelly attends the 2023 Sundance Film Festival Bad Behaviour Premiere at The Ray Theatre on January 21, 2023 in...
14/06/2024
SEATTLE ZTransform recently delivered AV and media facilities to Augustana University's highly anticipated Midco Arena. Despite challenging tie constraints,...
14/06/2024
LONDON A new report from Omdia finds that the global market for OLED materials is poised for a rebound after experiencing a deficit in recent years....
14/06/2024
WASHINGTON D.C. During the annual NextGen Broadcast Conference this week, the ATSC honored Dr. Sung-Ik Park of Korea's Electronics and Telecommunications Re...
14/06/2024
WUPPERTAL, Germany Riedel Communications has announced that TVMonaco, the first general-interest public television channel in Monaco, has selected Riedels Artis...
14/06/2024
Children's Digital Learning Facility REDEE Adopts Blackmagic Design Workflow...
14/06/2024
NUGEN Audio Releases NUtility Toolkit
Brie Clayton June 14, 2024
0 Comments
NUGEN Audio unveils its new NUtility Toolkit, which comprises its SigMod, ...
14/06/2024
HBO has announced that its high profile original drama series House of the Dragon has been renewed for a third season....
14/06/2024
OSLO Pixotope has announced the availability of Pixotope 24.1.0 and is reporting that the release includes the full integration of Unreal Engine 5.4, which open...
14/06/2024
LOS ANGELES Cineverse Corp. is reporting that its YouTube channels have passed the 10 million subscribers mark, thanks to the success of eight brands that have ...
14/06/2024
Ratings for the NBA Finals continue to improve with the average audience for NBA Finals Game 3 on ABC and ESPN up two percent from last year's Game 3, accor...
14/06/2024
Clear-Com is thrilled to announce that the highly anticipated Gen-IC Virtual Intercom, a revolutionary system combining the power of cloud production with Cle...
14/06/2024
Acronis, a global leader in cybersecurity and data protection, is pleased to introduce Acronis XDR the newest addition to the company's security solution po...
14/06/2024
Veset has announced that Veset AdWise is now available in AWS Marketplace. Veset AdWise is the advanced, cloud-based solution for real-time, in-video advertisin...
14/06/2024
Bedrock, the leading European streaming tech company, and Ease Live, an Evertz company providing innovative interactive TV technology, announce their newly form...
14/06/2024
V-Nova, a leading provider of data compression solutions, video compression technology, XR technology, AI acceleration and parallel processing for a multitude o...
14/06/2024
Triveni Digital today announced that Capitol Broadcasting Company owner and operator of WRAL-TV, WRAZ-TV, WILM-TV, and WNGT-TV in North Carolina has selecte...
14/06/2024
Riedel Communications today announced that TVMonaco, the first general-interest public television channel in Monaco, has selected Riedel s cutting-edge Artist i...
14/06/2024
Viaccess-Orca (VO), a global leader providing OTT and TV platforms, content protection, and advanced data solutions, announced today that pay-TV operator Orange...
14/06/2024
Pixotope, the leading software platform for end-to-end real-time virtual production solutions, today announced the availability of Pixotope 24.1.0. This release...
14/06/2024
NUGEN Audio unveils its new NUtility Toolkit, which comprises its SigMod, AB Assist, Jotter and Aligner plug-ins. Ideal for entry-level and professional audio p...
14/06/2024
Ross Video is excited to announce its participation in InfoComm 2024, held from June 12 to 14 at the Las Vegas Convention Center. This year, Ross Video is set t...
14/06/2024
Zixi, provider of the award-winning Software-Defined Video Platform (SDVP ) and the industry leader for enabling reliable, scalable and cost-efficient live vide...
14/06/2024
Beam Dynamics, leaders in technology lifecycle management, has implemented its Data Improvement Platform (DIP) at NMR Events, a major American industrial stagi...
14/06/2024
Tiffen welcomes the filmmaking community for its annual Tech Day '24 featuring the Stabilizer Expo, live equipment demos, and Tech Talks with renowned Opera...
14/06/2024
Excitement is building for the opening of Cine Gear Expo at the Warner Bros. Studios in Burbank. This year's expo holds much to look forward to from technol...
14/06/2024
The 38th Annual WRAL Azalea Celebration is now accepting applications from non-profits for the 2024 plant giveaway. Sponsored by WRAL-TV, MIX 101.5 WRAL-FM, FOX...
14/06/2024
Tee up a fun golf at American Tobacco. State of Golf, Downtown Durham's premier golf & sports simulator lounge opened on June 11, 2024. Get inspired by US O...
14/06/2024
Dr. Lenora Helm Hammonds Named Dean of the Professional Education Division A renowned jazz vocalist, educator, and Berklee alumna, Hammonds is known for her i...
14/06/2024
Joey Chestnut is a scratch for the Nathan's Famous Fourth of July International Hot Dog-Eating Championship, but he and another speed-eating luminary, Taker...
14/06/2024
Paula Ebben will anchor mornings with Chris Tanaka at WBZ Boston starting June 17. Ebben currently anchors evening news and anchored WBZ's morning news from...
14/06/2024
Rock'n Robin Productions, the production outfit run by Robin Roberts, has announced two executive hires. Reni Calister is the new chief content officer and ...
14/06/2024
When she was five years old, Veronica Miller (n e Teklai) and her family left their homeland of Eritrea, in the Horn of Africa, to escape an ongoing war with Et...
14/06/2024
Euro 2024: UEFA's technical broadcast operation By George Bevir
Tuesday, June 11, 2024 - 09:45
Print This Story
Leipziger Messe: Hall 4 of the venue w...
14/06/2024
Euro 2024: UEFA's live production plans By George Bevir
Tuesday, June 11, 2024 - 09:45
Print This Story
Euro 2024 kicks off on Friday evening (14 June...
14/06/2024
Euro 2024: UEFA's ENG crews at the ready By George Bevir
Tuesday, June 11, 2024 - 09:44
Print This Story
With UEFA set to deliver over 3,500 hours of ...
14/06/2024
FOX Sports' Wave of UFL Tech Innovation Crescendos With Championship Game Th...
14/06/2024
Breaking the Ice: Inside the NHL's Adventures in Live Cloud Production NHL's Grant Nodine and AWS's Andrew Reich offer a behind-the-scenes look By ...
14/06/2024
USGA Taps SMT for U.S. Open On-Course, Video-Production Services for 17th Year The sports-media-tech provider is distributing content to 30 displays and 650 TVs...
14/06/2024
FOX Sports Takes Virtual Production to New Heights With Groundbreaking Basilica...
14/06/2024
Back to All News
Britain's Quarter of a Billion Pound Bridgerton' Boost
Entertainment
14 June 2024
GlobalUnited Kingdom (Great Britain)
Link copie...
14/06/2024
By Craig Anderton
Announcement: The 2nd Edition of The Huge Book of Studio One Tips and Tricks is now available as a free download for owners of previous versi...
14/06/2024
NVIDIA today announced Nemotron-4 340B, a family of open models that developers ...