Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 34,080 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Showing posts with label Alzheimers treatment. Show all posts
Showing posts with label Alzheimers treatment. Show all posts
PrecivityAD2 is the first blood-based biomarker for people as young as 40 with cognitive symptoms
The FDA cleared the PrecivityAD2 blood test to help diagnose Alzheimer's disease as part of a standard clinical workup, C2N Diagnostics announced Thursday.
The test, which measures plasma amyloid beta and tau peptide ratios to assess the likelihood of brain amyloid plaques, is the first Alzheimer's blood-based biomarker for people as young as 40 with cognitive symptoms.
PrecivityAD2 is indicated for adults with signs or symptoms of cognitive impairment being evaluated for Alzheimer's or other forms of cognitive decline. It's intended to be used with a clinical assessment to help healthcare professionals identify patients with amyloid pathology, not as a screening or standalone diagnostic test.
The test uses high-resolution mass spectrometry to quantify Alzheimer's disease biomarkers in blood, producing an outcome called the amyloid probability score 2 (APS2). The APS2 incorporates the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non-p-tau217, combined with a plasma amyloid-beta 42/40 ratio, to rule in or rule out Alzheimer's disease.
In a validation study of 1,142 people with signs or symptoms of cognitive decline, PrecivityAD2 showed a 97.6% positive predictive value (rule-in) and a 93.1% negative predictive value (rule-out) to detect brain amyloid plaques using dual cutoffs measured against amyloid PET or cerebrospinal fluid testing, C2N reported. The test was effective at detecting plaques in a wide range of patients, including people with mild symptoms and those with more advanced cognitive impairment.
PrecivityAD2 showed consistent diagnostic performance as age increased and in people with comorbidities like atrial fibrillation, autoimmune or inflammatory disease, chronic heart failure or kidney disease, coronary heart disease, depression, diabetes, dyslipidemia, history of cancer, history of stroke or transient ischemic attack, hypertension, or obesity, the company added.
A recent study in Sweden showed the test was useful to help primary care physicians rule out Alzheimer's disease. Earlier research showed the APS2 score performed better than primary care doctors or dementia specialists in detecting Alzheimer's disease among people with cognitive symptoms.
In 2025, the FDA cleared two other diagnostic blood tests for Alzheimer's disease: one to help clinicians identify Alzheimer's in people with signs and symptoms, the other to rule out Alzheimer's disease in primary care.
Lab-developed tests not approved by the FDA are also on the market. Last year, the Alzheimer's Association issued guidance outlining sensitivity and specificity parameters for Alzheimer's blood tests to either triage or diagnose people with cognitive impairment.
An estimated 19 to 20 million U.S. adults 65 and older, and hundreds of thousands more between the ages of 45 and 65, have cognitive impairment and may benefit from an early diagnosis, C2N Diagnostics noted.
PrecivityAD2 can be ordered by healthcare professionals experienced in evaluating patients with cognitive impairment, the company stated. It currently is available as a lab-developed test; the FDA-cleared test version is expected to be available later this year.
With your risk of dementia post stroke, is your competent? doctor preparing testing for stroke patients to see if this would prevent Alzheimers'? NO? NOTHING DOING? PURE INCOMPETENCE THEN!
Your risk of dementia, has your doctor
told you of this? Your doctor is responsible for preventing this! Is
s/he willing to prevent this?
A blood-thinning medication already taken by millions of people for an irregular heartbeat may also be helping to slow cognitive decline in patients with Alzheimer’s disease, according to new research from Karolinska Institutet in Sweden.
The study, published in the European Heart Journal, found that people with both atrial fibrillation and Alzheimer’s disease who were treated with newer blood thinners known as NOACs unintentionally experienced a significantly slower rate of cognitive decline than those given the older drug named warfarin or no blood thinner at all.
“There are reasons to believe that the treatment could have a positive effect on cognition, for example by improving blood flow and reducing small-scale damage in the brain,” Maria Eriksdotter, a professor at Karolinska Institutet who led the study, said in a statement.
Newsweek reached out to Karolinska Institutet for more information.
Why the Two Conditions Are Often Linked
Atrial fibrillation, a common heart rhythm disorder among older adults, frequently occurs alongside Alzheimer’s disease.
Doctors typically prescribe blood-thinning medication to atrial fibrillation patients to lower their risk of blood clots. Earlier research had suggested that anticoagulant treatment might reduce the risk of developing dementia in the first place, but scientists knew far less about how these drugs affect people who already have Alzheimer’s.
Researchers drew on data from SveDem, Sweden’s national quality register for cognitive disorders and dementia, examining 7,308 people diagnosed with both atrial fibrillation and Alzheimer’s disease.
Participants were sorted into three matched groups: those taking NOACs, those taking warfarin, and those taking no anticoagulant medication at all. Cognitive function was tracked over time using the Mini-Mental State Examination (MMSE), a standard test used to measure memory and thinking skills.
What the Results Showed
Patients on NOACs saw their cognitive decline slow by just over 0.2 MMSE points per year compared with those on warfarin or no treatment at all.
The benefits extended beyond cognition. Patients treated with NOACs also had a lower risk of death, stroke, blood clots and fractures compared with those who received no anticoagulant treatment. Warfarin was also linked to lower risks of death, stroke and blood clots, but it came with a higher risk of major bleeding than NOACs.
England-based general practitioner, Dr Mohammad Bakhtiar, spoke with Newsweek about the findings.
“Over 7,000 people is large enough that the signal is hard to dismiss as noise,” he said. “That makes the data more reliable than the usual small clinic series.
“What I take from the study is encouraging evidence for the newer anticoagulants over warfarin in this group. The cognitive difference is modest, but it sits alongside fewer strokes, clots and deaths, and less major bleeding than warfarin. For GPs deciding between a NOAC and warfarin in someone with Alzheimer’s and atrial fibrillation, that is useful.”
The researchers cautioned that, because the study was observational, it cannot prove that the drugs directly caused the slower decline. Some factors that may have influenced both which drug a patient was prescribed and their eventual health outcomes could not be fully accounted for. Some patients also may have switched between medications during the course of the study, which followed participants over time. All in all, while they remain optimistic, they acknowledge the promising results require further studies.
“We should read observational studies cautiously,” Bakhtiar added. “People who get a NOAC are often different from people who get nothing. They may be fitter, better supported, or under more active specialist care. Some patients also switched drugs during follow-up.
“So, the honest line is association, not proof. NOACs were linked with slower decline. We do not know they caused it.”
He advises that patients excited by the news do not start, stop or switch their current medications because of this paper.
The study was funded by several organizations, including the Swedish Research Council, the Swedish Brain Foundation, CIMED, ALF project funding and Karolinska Institutet.
Reference
Eriksdotter, M., et al. (2026). Oral anticoagulants, cognition, and clinical outcomes in atrial fibrillation and Alzheimer’s disease: a Swedish nationwide study. European Heart Journal. https://doi.org/10.1093/eurheartj/ehag584.
An experimental drug might slow early Alzheimer’s disease by targeting a hallmark of the illness that researchers have historically had less success with: toxic tangles of tau proteins inside the brain.
Accumulations of these tau tangles and sticky clumps of the protein amyloid beta are the neurodegenerative disease’s defining features. In recent years, two drugs that clear amyloid plaques have been approved by the Food and Drug Administration—the first new Alzheimer’s therapies in about two decades. Meanwhile, many experimental treatments targeting tau have failed, despite research suggesting that tau tangles are a stronger predictor than amyloid of brain deterioration.
Now, findings from a mid-stage clinical trial presented on July 14 at the Alzheimer’s Association International Conference in London could change that. Researchers revealed that an experimental anti-tau drug slowed cognitive decline at a level on par with the approved anti-amyloid drugs—although puzzlingly, that result came about in the treatment group that received the lowest dose. The work offers hope for the treatment of a disease that affects more than seven million Americans ages 65 and older, though a larger follow-up study will need to confirm the therapy’s benefits.
“This is really quite promising if it were to hold up” in further testing, says Jessica Langbaum, senior director of Alzheimer’s prevention and research at the Banner Alzheimer’s Institute who wasn’t involved in the trial, to Lauran Neergaard at the Associated Press.
The drug, called diranersen, was developed by Biogen, a Massachusetts-based biotech company. It works by attaching itself to genetic instructions for making tau, forcing the brain to produce less of the protein.
In all three treatment groups, the drug lowered tau levels in brain and spinal fluid by 50 to 65 percent compared to the participants’ starting baseline. Brain imaging of 131 participants also showed decreases in tau tangles relative to baseline across all doses.
But the drug defied one of the researchers’ main expectations: that cognitive outcomes would strengthen with dose. In the trial, the lowest-dose group experienced the greatest slowing of cognitive decline—by 26 percent in one test—and the smallest decrease in tau levels. The middle-dose group’s cognitive decline slowed by 14 percent based on that test, and the highest-dose group’s slowed by 9 percent.
While many outside experts welcome the findings, they highlight the deviation from the expected dose-dependent response. And some participants who received higher doses suffered from a state of confusion for up to one week following injection. That’s why the findings represent “a double, not a home run,” says Adam Boxer, a neurologist at the University of California, San Francisco who is working on a different anti-tau therapy, to Jennie Erin Smith at Science.
Rob Howard, a psychiatrist at University College London who wasn’t involved in the study, explains to R.J. Mackenzie at Science News that the counterintuitive cognitive results could be due to the study’s small cohort or the drug’s small effect sizes.
The size of change in cognitive scores was “pretty tiny,” and it’s unclear how it would translate to patients in the real world, he adds. “It’s the age-old question: Are these clinically meaningful differences?”
What’s more, the side effect of confusion was unexpected, Boxer tells Science. It may have happened because the drug affected something it wasn’t supposed to, but a more troubling possibility is that it’s related to lowering tau, he says. “Maybe we can’t knock down tau without some effects.” Biogen, for its part, notes that the confused state was temporary.
“This was a well-tolerated trial where people wanted to continue on treatment,” neurologist Cath Mummery of University College London said as she presented the study at the conference, reports Andrew Joseph at STAT.
The company now plans to test diranersen in a late-phase clinical trial to see how it fares with a larger group of participants. And perhaps it could one day be tested in conjunction with amyloid-targeting drugs, Heather Snyder, a neuroscientist and senior vice president of medical and scientific relations at the Alzheimer’s Association, tells Science News. She notes that other trials are studying combinations of different anti-tau and anti-amyloid drugs.
“We are seeing the entire movement of thinking about these different targets and how [we can] start putting tau together with amyloid,” Snyder says.
Whoops, lecanemab is not for me. With my damaged brain
already running with millions to billions less neurons I'll pass on more
brain shrinkage. But I'm not medically trained so don't listen to me.
But there is a new and disturbing fly in the ointment.. A study published in the journal Neurology (March 27, 2023)
reveals that anti-amyloid drugs like lecanemab can cause brain
shrinkage. The researchers call this accelerated “brain atrophy.”
And this from the article means more reason not to do this. Caution is also advised for patients using anticoagulant medications because of an increased risk of intracerebral haemorrhage.
The US Food and Drug Administration (FDA) approved a new starting dosage regimen for the subcutaneous (SC) formulation of lecanemab-irmb (Leqembi IQLIK) for adult patients with Alzheimer’s disease. This approval allows individuals to begin treatment via home administration by themselves or a caregiver, marking a significant update from the previous requirement for an intravenous (IV) starting dosage.
Lecanemab-irmb is an amyloid beta-directed antibody indicated for patients at the mild cognitive impairment or mild dementia stage of Alzheimer’s disease with confirmed amyloid pathology. Before this decision, the SC formulation was only authorised as a maintenance option for patients who had already completed 18 months of IV therapy.
Although the SC formulation was not evaluated in separate large clinical outcome trials, its approval was supported by evidence demonstrating that it produced equivalent results in the body and similar reductions in amyloid plaques compared with the IV formulation.
Common side effects include headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA). ARIA is a known side effect of amyloid-targeting antibodies and typically presents as temporary brain swelling or small spots of bleeding. While often asymptomatic, ARIA can lead to headache, confusion, dizziness, and nausea, and may infrequently cause life-threatening brain oedema.
The prescribing information includes a boxed warning regarding ARIA risks. The FDA noted that patients homozygous for the ApoE ε4 allele have a higher incidence of serious ARIA compared with heterozygotes and non-carriers. Consequently, testing for ApoE ε4 status should be performed before initiating treatment.
Additional adverse reactions associated with SC administration include injection-site reactions such as redness, swelling, and pain. Caution is also advised for patients using anticoagulant medications because of an increased risk of intracerebral haemorrhage.
The approval was granted to Eisai under a priority review designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
The calling card of Alzheimer’s disease is a buildup of misfolded amyloid protein in the brain, but many medicines struggle to penetrate the barrier protecting the mind from outside interference. A new study suggests that crossing the blood-brain barrier might not be necessary at all to clear amyloid plaques—and that a one-time gene therapy could one day prove an effective treatment for the devastating neurodegenerative disease.
In a study led by researchers at the Army Medical University in Chongqing, China, a gene for a protective protein was successfully delivered to mice, leading to reduced plaques and cognitive improvements. Unlike other gene therapy approaches for Alzheimer’s, this technique uses a standard liver-targeted vector rather than trying to get into the brain.
The results were published in Neuron on May 6.
It has long been known that a variant of the apolipoprotein E gene, known as APOE4, is associated with a higher risk of developing Alzheimer’s disease. But more recently, protective versions of the gene have also been identified, most notably a variant called APOE3 Christchurch.
APOE3Ch’s potential became more widely recognized when it was found in a woman who also had two copies of a mutated presenilin 1 gene. Mutations in the gene are known to cause early-onset Alzheimer’s disease that typically leads to cognitive impairment beginning around age 44. But because she also had two copies of APOE3Ch, she didn’t begin developing symptoms until her 70s.
“Clinical studies have shown that APOE3Ch can delay the onset age and pathological progression of [Alzheimer’s],” Dr. Zhong-Yuan Yu, one of the new study’s lead authors, told Fierce Biotech. The gene has also shown past promise in animal studies, Yu added.To see if APOE3Ch could protect those not born with it, the researchers packaged the gene into a viral vector and injected it into male mice with the risky APOE4 variant. APOE is also expressed in the liver, and that’s where the gene therapy made its way. Treated mice showed smaller amyloid plaques, less brain inflammation and performed better in a maze-based memory test.
The findings surprised Jason Ulrich, Ph.D., a neurologist at Washington University in St. Louis, who wasn’t involved with the study.
“It is somewhat surprising to me, at least that changes in amyloid were observed using this approach,” Ulrich told Fierce. He noted that past studies have found knocking out APOE in the liver had no effect on brain amyloid, and even that expressing the bad form of APOE, APOE4, in the organ didn’t lead to more APOE crossing into the brain.
So, how is APOE3Ch in the liver having an effect? By clearing amyloid out of the blood, Yu told Fierce. The gene variant helps the liver and immune cells called monocytes remove amyloid from the blood, he said, and because the brain and the blood maintain an amyloid balance, this leads to an exodus of the disease-causing protein from the brain.
The researchers' next plan is to test the approach in non-human primates before moving into clinical trials, Yu said.
The liver is a standard organ to target for gene therapy, and is much easier to reach than other brain-targeting approaches that have been tried for Alzheimer’s. But Ulrich said he needs more information before he will endorse a liver-targeting gene therapy for the notorious neurodegenerative disease.
“I would want to know a lot more about the mechanism,” he said. “It's not clear from this study that APOE3Ch is special, as other APOE isoforms such as APOE2 or APOE3 ‘Jacksonville’ weren't explored.”
Summary: Current Alzheimer’s treatments typically require frequent, high-dose infusions of monoclonal antibodies to slow cognitive decline. But researchers have engineered a potentially game-changing alternative: CAR-astrocytes. Taking inspiration from CAR-T cell therapy used in cancer, scientists used a harmless virus to “reprogram” astrocytes—the most abundant cells in the brain—with a specialized “homing device.”
These modified cells, dubbed “super cleaners,” are designed to specifically target and engulf amyloid-beta plaques. In a study published in Science, a single injection of these CAR-astrocytes completely prevented plaque development in young mice and cut existing plaque levels in half in older mice.
Key Facts
The “Homing Device”: Researchers equipped astrocytes with a Chimeric Antigen Receptor (CAR) that allows them to identify and “grab” amyloid-beta proteins for destruction.
Single-Shot Potential: Unlike monthly antibody infusions, this cellular immunotherapy showed massive effectiveness with just a single injection in mouse models.
Prevention & Treatment: When given before plaques formed, the therapy kept the brain plaque-free. In brains already saturated with amyloid, it reduced the plaque load by 50% within three months.
Reducing the Burden: Traditionally, microglia (the brain’s immune cells) handle “trash removal,” but they become overwhelmed in Alzheimer’s. CAR-astrocytes provide much-needed reinforcement.
Beyond Alzheimer’s: The team believes this technology could be adapted to target brain tumors by switching the CAR device to recognize cancer markers instead of amyloid.
Source: WUSTL
The new generation of Alzheimer’s disease drugs — the first proven to change the course of the disease — typically extend independent living for patients by 10 months. Called monoclonal antibodies, they reduce the accumulations of a harmful protein, amyloid, in the brain and require high-dose, once- or twice-monthly infusions of the medication.
Now, to reduce the frequency of treatment and potentially improve the efficacy of an anti-amyloid therapy, researchers at Washington University School of Medicine in St. Louis have engineered a new cellular immunotherapy that requires just a single injection to prevent amyloid plaques from developing when given before plaques start to form in mice. Furthermore, a single treatment in mice that had already developed plaques cut the amount of amyloid plaques in half.
New research demonstrates the first successful engineering of astrocytes to specifically target and remove harmful amyloid-beta plaques in the brain. Credit: Neuroscience News
The study was published March 5 in Science.
Like CAR-T cell therapies used for cancer treatment, in which T cells of the immune system are genetically modified to attack cancer cells, this new approach equips cells — in this case, brain cells called astrocytes — with a CAR homing device to grab onto a target for destruction. These new CAR-astrocyte cells have features that transform them into super cleaners that remove damaging proteins from the brain that play a role in cognitive decline.
“This study marks the first successful attempt at engineering astrocytes to specifically target and remove amyloid beta plaques in the brains of mice with Alzheimer’s disease,” said the study’s senior author, Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology at WashU Medicine.
“Although more work needs to be done to optimize the approach and address potential side effects, these results open up an exciting new opportunity to develop CAR-astrocytes into an immunotherapy for neurodegenerative diseases and even brain tumors.”
Removing brain waste
Alzheimer’s disease starts with a sticky protein called amyloid beta that builds up into plaques in the brain, setting off a chain of events that results in brain atrophy and cognitive decline.
Microglia, immune cells that reside in the brain, are responsible for removing brain waste but can become dysfunctional when overwhelmed in the context of neurodegenerative disease.
To reduce the cleaning burden on microglia, first author Yun Chen, PhD, then a graduate student in the labs of Colonna and David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology at WashU Medicine, transformed astrocytes, the most abundant cell type in the brain, into amyloid-cleaning machines.
He custom-designed and delivered a gene to astrocytes that codes for the chimeric antigen receptor (CAR) via a harmless virus injected into mice. The CAR, now present on the surface of astrocytes, enabled the cells to capture and engulf amyloid beta proteins.
With their newly acquired ability, the astrocytes — generally responsible for keeping the brain tidy — concentrated their efforts on only cleaning amyloid beta plaques in mice prone to its buildup.
Mice carrying genetic mutations that increase people’s risk of developing Alzheimer’s disease develop amyloid beta plaques that saturate the brain by six months of age. Chen, now a postdoctoral researcher in the Holtzman lab, injected two groups of mice with the virus carrying the CAR-expressing gene: young mice before they developed plaques and older mice with brains saturated with plaques. Then he waited three months.
As the younger mice aged, the CAR-astrocytes prevented amyloid beta plaque development. At nearly six months of age, when untreated mice normally have brains saturated with harmful plaques, brains of treated mice were plaque-free. Meanwhile, older mice with plaque-saturated brains at the time of treatment saw a 50% reduction in the amount of amyloid beta plaques compared to mice receiving an injection of a virus lacking the CAR gene.
The researchers have filed a patent, with help from the Office of Technology Management at WashU, related to the approach used to engineer CAR-astrocytes.
“Consistent with the antibody drug treatments, this new CAR-astrocyte immunotherapy is more effective when given in the earlier stages of the disease,” said Holtzman, who is a co-author on the paper.
“But where it differs, and where it could make a difference in clinical care, is in the single injection that successfully reduced the amount of harmful brain proteins in mice.”
In future studies, the authors aim to continue improving their CAR-astrocyte immunotherapy by fine-tuning its design to better target harmful proteins, while ensuring no harmful effects on normal brain cell functions.
Additionally, by adjusting the CAR homing device to recognize specific markers on brain tumors, they could potentially switch astrocytes’ function from cleaning up debris to directly killing tumor cells. Such an approach could offer a promising new way to treat brain tumors and other central nervous system diseases.
Key Questions Answered:
Q: Is this like the “cancer-killing” T-cell therapy but for the brain?
A: Exactly! It uses the same core technology (CAR). Instead of teaching immune cells to find and eat cancer, scientists are teaching brain cells (astrocytes) to find and eat the “sticky” plaques that cause Alzheimer’s.
Q: Why use astrocytes instead of just giving more antibodies?
A: Antibodies have to be pumped into the body constantly and don’t always cross into the brain efficiently. By “upgrading” the cells already inside your brain, you create a permanent cleaning crew. This study showed that one single “upgrade” was more effective and lasted longer than current methods in mice.
Q: When will this be available for humans?
A: We are still in the early stages. While the results in mice are “plaque-free” spectacular, the researchers need to ensure these super-cleaners don’t accidentally eat healthy brain parts or cause inflammation. Human trials are the next major hurdle.
Editorial Notes:
This article was edited by a Neuroscience News editor.
Journal paper reviewed in full.
Additional context added by our staff.
About this neurology and Alzheimer’s disease research news
Author:Jessica Church Source: Washington University Contact: Jessica Church – Washington University Image: The image is credited to Neuroscience New
Summary: Researchers discovered a powerful new drug target that could revolutionize how we treat Alzheimer’s disease. By focusing on an enzyme called IDOL, researchers found they could substantially reduce the buildup of toxic amyloid plaques in the brain.
Unlike current treatments that primarily focus on clearing existing plaques, targeting IDOL in neurons also lowers levels of the APOE protein—the strongest genetic risk factor for the disease—and boosts the brain’s natural resilience to cognitive decline. This multi-pronged approach not only clears the “trash” from the brain but also strengthens the connections between neurons, offering hope for a more effective way to freeze the disease’s progression.
Key Facts
Targeting Neuronal IDOL: Removing the IDOL enzyme from brain neurons significantly reduces amyloid plaque load and improves communication between nerve cells.
Resilience Booster: Deleting this enzyme increases the levels of receptors that regulate lipid metabolism, which has been shown to provide cognitive resilience even in patients with high plaque levels.
APOE Reduction: The study found that targeting IDOL also lowers levels of APOE, the protein variant (APOE4) that serves as the most significant risk factor for late-onset Alzheimer’s.
Source: Indiana University
Indiana University School of Medicine scientists have identified a promising drug target for Alzheimer’s disease.
The team found that removing an enzyme from neurons in the brain substantially reduces amyloid plaques — a hallmark characteristic of the disease — and may provide further resilience against disease progression.
Over the past few years, the U.S. Food and Drug Administration has approved two disease-modifying drugs to treat Alzheimer’s disease. The drugs, lecanemab and donanemab, remove the buildup of amyloid plaques in the brain and can “freeze” a person in their current functional state.
By hitting the IDOL enzyme, researchers can lower the impact of the APOE4 protein—the most significant genetic risk factor for Alzheimer’s. Credit: Neuroscience News
The team of researchers at the IU School of Medicine, led by Hande Karahan, PhD, and Jungsu Kim, PhD, say targeting this enzyme, called IDOL, in neurons can be a new way to remove amyloid plaques and improve communication between neurons and lipid metabolism in the brain.
“What makes this exciting is that we now have a specific target that could lead to a new type of treatment,” said Kim, the P. Michael Conneally Professor of Medical and Molecular Genetics.“We believe that IDOL will provide us with an alternative strategy to treat Alzheimer’s disease. Targeting enzymes in drug development offers key advantages due to their well-defined active sites or ‘pockets’ where drugs can attach and block their activity. This precision means we can design molecules that hit the right target with minimal side effects.”
In the study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the researchers generated two different animal models of Alzheimer’s disease by deleting the IDOL gene in the brain from either within neurons or microglia, the brain’s immune cells.
Karahan, assistant research professor of medical and molecular genetics, said they expected microglia to be the major driver of removing amyloid plaques because immune cells are key players in clearing amyloid and are the main cell type that produces IDOL in the brain.
Deletion of IDOL neurons not only reduced plaques, Karahan said, but it also reduced levels of a protein called apolipoprotein E, or APOE, that is associated with Alzheimer’s disease; one of the protein’s variants, APOE4, is the strongest risk factor for late-onset Alzheimer’s disease. APOE also plays a critical role in lipid metabolism, Karahan said.
The team also discovered that levels of receptors that can regulate APOE and amyloid plaques in the brain increased when the enzyme was removed from neurons.
These receptors have a critical role in lipid metabolism and healthy neuronal communication. Karahan said a recent study shows that activating a pathway, which is also regulated by these receptors, provides resilience to cognitive decline in Alzheimer’s patients who have high amounts of plaques.
“This is especially important from a clinical perspective because patients are usually diagnosed with the disease after accumulating substantial amyloid plaque load in the brain. Not only decreasing amyloid levels but also increasing resilience to these pathological changes could maximize clinical benefits,” Karahan said.
“Targeting neuronal IDOL may offer multiple therapeutic benefits in Alzheimer’s disease by simultaneously reducing amyloid burden while enhancing neuroprotective effects.”
Kim said the team will next work on a few strategies targeting the enzyme to develop drugs for treating Alzheimer’s disease, adding it’s important to assess the safety of compounds and their functional effects in preclinical models. Kim said they’ll also determine whether IDOL inhibition preserves synaptic connections and mitigates tau pathology in Alzheimer’s disease.
Key Questions Answered:
Q: We already have drugs that clear amyloid plaques—why is this different?
A: While current drugs like lecanemab and donanemab focus on clearing existing plaques, targeting the IDOL enzyme does something extra: it builds resilience. It’s like not only taking out the trash but also upgrading the building’s security system. By improving lipid metabolism and neuronal communication, this method helps the brain stay functional even if some plaques remain.
Q: What is the “APOE connection” and why does it matter?
A: APOE4 is the strongest genetic risk factor for Alzheimer’s. This study discovered that removing the IDOL enzyme naturally lowers APOE levels. By hitting both the plaques and the underlying genetic risk protein simultaneously, researchers may have found a way to attack the disease from two sides at once.
Q: Could this lead to a pill for Alzheimer’s?
A: That’s the goal. Because IDOL is an enzyme with a well-defined “pocket” where a drug can attach, it is a perfect candidate for drug development. Scientists are now working on molecules that can block this enzyme’s activity, which could eventually lead to a treatment that is more precise and has fewer side effects than current options.
Editorial Notes:
This article was edited by a Neuroscience News editor.
Journal paper reviewed in full.
Additional context added by our staff.
About this Alzheimer’s disease and neuropharmacology research news
Author: Rory Appleton Source: Indiana University Contact: Rory Appleton – Indiana University Image: The image is credited to Neuroscience News
