In 2020, over 55 million people worldwide were living with Alzheimer’s disease, a chronic neurodegenerative disease that is characterized by progressive cognitive decline, memory loss, and behavioral changes. The disease pathology involves the accumulation of proteins in the brain, amyloid-beta and tau, which leads to irreversible neuronal damage and cell death, but the exact cause still isn’t known. As one of the most common forms of dementia, Alzheimer’s disease predominantly occurs in older adults (over 65 years old), but about 5% of cases can present earlier, usually related to genetic predispositions. By 2050, the United States (US) National Institute on Aging estimates 16% of the world population will consist of older adults and the number of individuals living with dementia globally is expected to triple to 152 million by this time.  

Recognizing this neurodegenerative disease as a major global health challenge, World Alzheimer’s Month seeks to educate people about the impact of Alzheimer’s and the importance of early diagnosis and intervention. As we approach World Alzheimer’s Day on September 21, TFS HealthScience (TFS) Neuroscience CRO (Contract Research Organization) is joining the fight against Alzheimer’s disease. To show our support, this article highlights ten key advances in the field of Alzheimer’s research, from promising clinical trials and new drug approvals to novel biomarker and diagnostic discoveries.  

Keep reading and join TFS’s efforts to support World Alzheimer’s Month 2024! 

 

September Marks the Annual World Alzheimer’s Month 

Every year in September, the field of neuroscience turns purple as we observe World Alzheimer’s Month, an initiative that serves to change perceptions and increase existing public knowledge around Alzheimer’s disease and dementia. This year’s campaign will continue with the mission to challenge why so many people still wrongly believe that dementia is a part of normal aging. A significant highlight of the month is World Alzheimer’s Day, which takes place on September 21st. Every year, people around the world come together to show their support for individuals living with Alzheimer’s and their caregivers, as well as advocating for policy changes and increased funding for research. The campaign will also emphasize the importance of brain health and encourage individuals to adopt lifestyle changes that may reduce the risk of developing dementia. 

 

Top 10 Advances in Alzheimer’s Research 

Alzheimer’s disease causes significant physical, emotional, and socioeconomic burdens on patients and their families, making it an ongoing challenge for the clinical research community. However, the field is seeing a recent expansion in therapeutic advances and innovative trials, providing new hope for improving our ability to understand and treat this condition.  

Here, we spotlight 10 key advances in Alzheimer’s research, including novel biomarker discoveries, diagnostic innovations, advances in immunotherapy, and promising ongoing clinical trials.  

 

1. US FDA Approves the First Disease-Modifying Treatment for Alzheimer’s Disease

Drug Name: Aducanumab (Aduhelm®) 

Manufacturing Company: Biogen (Cambridge, Massachusetts) 

Approval Date: June 7, 2021 

Three years ago, Biogen’s aducanumab (Aduhelm®) marked a significant breakthrough in the treatment of Alzheimer’s disease. Approved by the US Food and Drug Administration (FDA) in June 2021, aducanumab is the first disease-modifying therapy for AD and the first new treatment to reach the market since 2003. Aducanumab is a human IgG1 anti-Aβ monoclonal antibody that targets and reduces amyloid beta plaque in the brain, a hallmark of AD.  

The drug’s approval was based on three studies involving 3,482 patients, which demonstrated a significant dose-and time-dependent reduction in amyloid beta plaque in treated patients compared to the control group. Aducanumab is indicated for the treatment of patients with early Alzheimer’s disease, including  those with mild cognitive impairment and mild dementia. It was granted approval under the FDA’s” accelerated approval pathway” and “Fast Track” designations. Read the full FDA press release here. 

 

2. US FDA Approves the First Drug Shown to Slow Disease Progression in Alzheimer’s

Drug Name: Lecanemab (Leqembi®) 

Manufacturing Companies: Eisai (Japan) and Biogen (Massachusetts) 

Approval Date: July 6, 2023 

As of a few years ago, the therapeutic landscape of Alzheimer’s disease was limited to drugs that could only address the symptoms of the condition, but none that showed potential in slowing disease progression. In July 2023, Eisai’s lecanemab changed this, becoming the first drug to demonstrate a slowdown in the progression of Alzheimer’s disease. This humanized IgG1 monoclonal antibody works by targeting and removing beta-amyloid plaques in the brain commonly seen in patients with Alzheimer’s.  

Its pivotal clinical trials demonstrated that lecanemab could slow cognitive decline by approximately 27% over 18 months, potentially offering patients more quality time with their families. The drug initially received accelerated approval in January 2023 based on its ability to remove beta-amyloid from the brain, but it was fully approved in July to reflect the FDA’s assessment of its cognitive benefits. Read the full FDA press release here. 

 

3. US FDA Approves Latest Alzheimer’s Drug to Slow Cognitive and Functional Decline

Drug Name: Donanemab (Kisunla™) 

Manufacturing Company: Eli Lilly and Company (Indiana) 

Approval Date: July 2, 2024 

Donanemab is a once-monthly injection that was recently approved in July 2024 for treating adults with early symptomatic Alzheimer’s disease, including those with mild cognitive impairment and mild dementia. In the key TRAILBLAZER-ALZ 2 Phase 3 study, those with low to medium tau protein levels treated with donanemab showed a 35% slower decline in memory, thinking, and daily functioning compared to placebo. Donanemab also showed impressive results in reducing amyloid plaques over time, with an average reduction of 61% at 6 months, 80% at 12 months, and 84% at 18 months.  

Similar to other disease-modifying drugs approved for Alzheimer’s disease, donanemab works by helping the body eliminate excessive amyloid buildup in the brain. However, it also has a unique objective in that it aims to reduce amyloid plaques to levels consistent with a visually negative PET scan, at which point patients can discontinue treatment. This approach offers renewed hope for slowing disease progression, as well as presenting a more targeted and potentially cost-effective treatment strategy for patients living with Alzheimer’s. Read the full FDA press release here. 

 

4. New Alzheimer’s Treatment Shows Early Promise in First Human Clinical Trial

Drug Name: LM11A-31 

Research Affiliations: Stanford University (California), University of California, San Francisco (California), Western University (Canada) 

Publication: Shanks et al. Nat Med 30, 1761–1770 (2024). https://doi.org/10.1038/s41591-024-02977-w 

LM11A-31 targets the P75 neurotrophin receptor (P75NTR) in the brain, which plays a crucial role in regulating cell survival, growth, and death. By enhancing the passage of signals that promote cell survival and growth, LM11A-31 aims to improve the brain’s resilience to Alzheimer’s-related changes. In this joint Phase 2A clinical trial for mild to moderate Alzheimer’s disease, the safety and tolerability of this agent was assessed in 242 human subjects across five European countries. The researchers also collected data on various markers of brain pathology to evaluate the drug’s potential impact on disease progression.  

The study revealed significant changes in two synaptic biomarkers from cerebrospinal fluid (CSF) within just six months, which is encouraging because most phase 3 trials for Alzheimer’s treatments typically span about two years. This trial also marks a significant milestone in Alzheimer’s clinical research because it represents the first time the P75 neurotrophin receptor has been targeted in human patients after a decade of preclinical work. Read the full study published in Nature Medicine here. 

 

5. GLP-1 Drug Liraglutide May Protect Against Dementia

Drug Name: Liraglutide  

Research Affiliations: Imperial College London (UK)  

AAIC® Proposal ID: 89799 

Researchers from the Imperial College London presented promising Phase 2B clinical trial data from the ELAD study in July 2024 at this year’s Alzheimer’s Association International Conference® (AAIC®). The research focused on the potential benefits of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in slowing cognitive decline in patients with mild Alzheimer’s. This double-blind, placebo-controlled trial involved 204 patients across 24 clinics in the United Kingdom (UK) with participants receiving either liraglutide or a placebo daily for one year.  

Although the study didn’t meet its primary endpoint of changes in cerebral glucose metabolic rate, the liraglutide cohort had an 18% slower decline in cognitive function compared to the placebo group. MRI scans also found that these patients experienced nearly 50% less volume loss in crucial brain areas responsible for memory, language, and decision-making. Liraglutide, which is already used to manage diabetes and promote weight loss, is being investigated further for its potential neuroprotective effects. Read the full abstract here. 

 

6. Alzheimer’s Disease Blood Test Could Improve Diagnosis in Primary Care

Product Name: PrecivityAD2 test (known as “APS2”) 

Research Affiliations: Lund University (Sweden) 

Publication: Palmqvist et al. JAMA: e2413855 (2024). Online ahead of print. doi: 10.1001/jama.2024.13855 

The 2024 Alzheimer’s Disease Facts and Figures report indicates that dementia is often underdiagnosed, and even when diagnosed, many patients remain unaware or uninformed of their condition. This underscores the need for diagnostic blood tests for Alzheimer’s that can improve early diagnosis and maximize the opportunity for patients to access Alzheimer’s treatments as early as possible, potentially leading to better outcomes. A large study presented recently at AAIC® 2024 showcased the superiority of the PrecivityAD2 test (APS2) blood test in detecting Alzheimer’s more accurately than traditional diagnostic methods used by primary care doctors and specialists.  

In 1,213 patients, the APS2 demonstrated around 90% accuracy in identifying Alzheimer’s disease among 698 patients seen at memory clinics, compared to specialists’ 73% accuracy. Similarly, in primary care settings with 515 patients, APS2 maintained its 90% accuracy while primary care physicians achieved 63% accuracy. Notably, the APS2 test exhibited high accuracy even in patients with comorbidities such as kidney disease, which are common in older patients seen by primary care physicians. Read the full study published in The Journal of the American Medical Association here. 

 

7. Pilot Study Shows Diagnostic Potential of Novel Blood Biomarker in Alzheimer’s

Study Name: Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer’s disease 

Research Affiliations: University of Melbourne (Australia) 

Publication: Mahan et al. Metallomics: mfae038 (2024). Online ahead of print. doi: 10.1093/mtomcs/mfae038 

Recent research from the University of Melbourne showcases a potentially promising new method for early diagnosis of Alzheimer’s disease. The study, published online in Metallomics in August 2024, focuses on analyzing AD biomarkers, specifically the levels of potassium isotopes, in blood serum. The researchers compared blood serum samples from 10 healthy individuals and 10 AD patients, demonstrating the test’s ability to differentiate between the two groups. Unlike protein-based diagnostics, this inorganic biomarker approach avoids sample stability issues, making it more reliable and scalable. Overall, this minimally invasive blood test shows promise for detecting Alzheimer’s before the onset of cognitive decline or other common symptoms, which would offer a significant advantage over current diagnostic methods. Earlier detection not only increases a patient’s chance of receiving timely treatment, but also expands their eligibility for a wider range of clinical trials. Read the full study published in Metallomics here. 

 

8. First FDA-Authorized In Vitro Diagnostic Test for Alzheimer’s Available in the US

Product Name: Lumipulse G beta-Amyloid Ratio (1-42/1-40) in vitro diagnostic test  

Manufacturing Company: Fujirebio Diagnostics, Inc. 

Approval Date: May 5, 2022 

In May 2022, Fujirebio received De Novo marketing authorization De Novo marketing authorization from the US FDA for their Lumipulse® G β-Amyloid Ratio (1-42/1-40) in vitro diagnostic test. This test is designed to help assess β-Amyloid pathology in patients being evaluated for Alzheimer’s disease and other conditions with cognitive decline. As the first FDA-authorized test of its kind in the US, it offers a more accessible and less expensive alternative to the current standard of amyloid positron emission tomography (PET) brain imaging. It could potentially also improve the accuracy of early Alzheimer’s diagnosis where traditional cognitive tests alone have been shown to be incorrect in approximately 50-60% of patients.  

To detect the presence of β-Amyloid plaques in the brain, the Lumipulse test proximally measures the concentrations of β-Amyloid 1-42 and β-Amyloid 1-40 in cerebrospinal fluid to calculate a ratio. Although, Fujirebio emphasized that it is not intended to be used as a standalone diagnostic tool; instead, clinicians should interpret results from this test in conjunction with full information from comprehensive clinical evaluation in patients. Read the full press release here. 

 

9. Oral Therapeutic Agent Shows Encouraging Results in Phase 2/3 Alzheimer’s Trial

Drug Name: Buntanetap  

Manufacturing Company: Annovis Bio 

Clinical Trial ID: NCT05686044 

In results recently presented at AAIC® 2024, Annovis Bio reported promising results of butanetap, an oral therapy candidate for Alzheimer’s and Parkinson’s, from its ongoing Phase 2/3 controlled clinical trial. It demonstrated comparable safety and effectiveness in people with early Alzheimer’s disease, regardless of their APOE4 genetic status, which is especially important because APOE4 is a major risk factor for Alzheimer’s and can affect treatment safety.  

In patients with mild Alzheimer’s, all three doses of buntanetap resulted in significant improvements in cognitive function over time, with the 15 mg and 30 mg doses showing particularly notable improvements compared to the placebo. The drug also led to a reduction in total tau protein levels, suggesting it may have potential disease-modifying benefits. Annovis Bio plans to discuss these findings with the FDA and move forward with a larger Phase 3 study to further investigate buntanetap’s potential to modify the course of Alzheimer’s disease. If successful, buntanetap could become the first safe and convenient oral therapy that both provides symptomatic relief and slows disease progression in Alzheimer’s patients. Read the full article here. 

 

10. Releasing Immune Cells into the Brain May Help Slow Alzheimer’s Progression

Study Name: Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model 

Research Affiliations: Washington University School of Medicine (Missouri) and Zhejiang University School of Medicine (China) 

Publication: Hou et al. Sci Transl Med 16, eadj9052 (2024). doi: 10.1126/scitranslmed.adj9052. 

A study published earlier this year showcased the possibility of utilizing the brain’s natural immune cells, microglia, to clear amyloid plaques more effectively along with the role of apolipoprotein E (APOE) in this process. These microglia typically form barriers around plaques and can destroy them directly, but their function is impaired in Alzheimer’s patients. APOE4 is considered a major risk factor for Alzheimer’s and is known to be able to inactivate microglia by binding to their surface.  

Their research found elevated levels of LILRB4 receptors in brain tissue samples from Alzheimer’s patients and experimental mouse models demonstrated that an antibody targeting the LILRB4 receptor could block the interaction between APOE and LILRB4, allowing microglia to clear amyloid plaques more efficiently. However, further research is needed to understand the impact on tau protein tangles and potential health risks associated with this approach. Regardless, this report suggests that immunotherapies designed to target microglia activation could be a viable treatment strategy for Alzheimer’s and even other neurodegenerative conditions characterized by toxic debris in the brain, such as Parkinson’s disease and Huntington’s disease. Read the full study published in Science Translational Medicine here. 

 

Conclusion 

In conclusion, the field of neuroscience and Alzheimer’s clinical research is witnessing a major expansion in recent years in terms of innovations and new discoveries. These include three new disease-modifying agents now approved by the US FDA (aducanumab [2021], lecanemab [2023], and donanemab [2024]), diagnostic advances in detecting Alzheimer’s disease earlier (PrecivityAD2 blood test), and the potential of potassium isotope ratios as a novel blood biomarker for early diagnosis. Several more clinical trials are also underway, investigating other therapies, such as LM11A-31 and the GLP-1 receptor agonist, liraglutide. Each of these advancements represents significant progress in Alzheimer’s research, offering new hope for early diagnosis, treatment, and potentially slowing the progression of the disease.
 

As we approach World Alzheimer’s Day on September 21, join TFS in supporting the work of organizations like the Alzheimer’s Association and Alzheimer’s Disease International to raise awareness about stigma and challenges in this disease. Visit the Alzheimer’s Disease International website here to learn more about the 2024 campaign and how you can help bring attention towards those in their community that are affected by Alzheimer’s disease and other types of dementia. 

 

About TFS Neuroscience CRO 

Discover how TFS Neuroscience is paving the way for advancements in Alzheimer’s research with their expert team and innovative clinical solutions. By partnering with academic institutions and patient advocacy groups, they can offer sponsors comprehensive access to industry experts, as well as efficient patient-focused studies. Learn more about how TFS can support your Alzheimer’s clinical trials! Visit our landing page or contact a TFS representative today. 

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