“Our study is the first to clearly demonstrate how this anti-amyloid antibody therapy works in Alzheimer’s disease. We show that the therapy’s efficacy relies on the antibody’s Fc fragment, which activates microglia to effectively clear amyloid plaques,” says Dr. Giulia Albertini, co-first author of the study. “The Fc fragment works as an anchor that microglia latch onto when they are near plaques, as a consequence of which these cells are reprogrammed to clear plaques more efficiently.”

Alzheimer’s Disease and the Role of Microglia

More than 55 million people worldwide live with Alzheimer’s disease, which is driven by the buildup of amyloid plaques in the brain. These toxic protein clusters damage neurons and eventually lead to dementia. Although microglia naturally gather around these plaques, they are typically unable to remove them effectively. In response, researchers have been developing treatments aimed at restoring this essential immune function.

Antibody Therapy and the Fc Fragment

Lecanemab is one of the therapies designed to target amyloid-beta plaques and slow disease progression, and it has already received FDA approval. However, side effects have limited its overall benefit, and until now, its exact mode of action remained unclear.

Antibodies are made up of two main parts. One part binds to a specific target such as amyloid plaques, while the other part, the Fc fragment, signals the immune system. Earlier research suggested that microglia play a role in clearing plaques, but direct proof linking their activity to lecanemab’s effectiveness was missing. Some scientists had also proposed that plaque removal could occur without involvement of the Fc fragment. The team led by Prof. Bart De Strooper demonstrated that this fragment is essential, as microglia only responded when it was intact and functional.

To investigate this, researchers used a specially designed Alzheimer’s mouse model that included human microglial cells. This allowed them to closely observe how lecanemab interacts with human immune cells and promotes plaque clearance. When the Fc fragment was removed, the antibody no longer had any effect.

“The fact that we used human microglia within a controlled experimental model was a major strength of our study. This allowed us to test the very antibodies used in patients and observe human-specific responses with unprecedented resolution,” adds Magdalena Zielonka, co-first author.

Inside the Brain’s Plaque-Clearing Process

The team then examined how activated microglia actually remove amyloid plaques in this hybrid model. They identified key cellular processes involved in this cleanup, including phagocytosis and lysosomal activity. These processes were only triggered when the Fc fragment was present. Without it, the microglia remained inactive.

Using advanced techniques such as single-cell and spatial transcriptomics, the researchers also identified a specific gene activity pattern in microglia associated with effective plaque removal. This pattern included strong expression of the gene SPP1 and was uncovered using NOVA-ST, a method developed by the Stein Aerts lab (VIB-KU Leuven).

Toward Safer and More Effective Alzheimer’s Treatments

By defining the exact microglial program responsible for clearing plaques, the findings point toward new strategies for treating Alzheimer’s disease. Future therapies may be able to activate microglia directly, without relying on antibodies.

“This opens doors to future therapies that may activate microglia without requiring antibodies. Understanding the importance of the Fc fragment helps guide the design of next-generation Alzheimer’s drugs,” concludes Prof. Bart De Strooper.

The research conducted at the VIB-KU Leuven Center for Brain & Disease Research was supported by the European Research Council (ERC), Alzheimer’s Association USA, Research Foundation Flanders (FWO), Queen Elisabeth Medical Foundation for Neurosciences, Stichting Alzheimer Onderzoek — Fondation Recherche Alzheimer (STOPALZHEIMER.BE), KU Leuven, VIB, and UK Dementia Research Institute University College London.

The study is the first to quantitatively examine uncertainty in the birefringence angle. This measurement is important because it may provide clues about unknown physical theories that violate the universe’s left right symmetry. It could also help scientists better understand dark matter and dark energy.

A Subtle Twist in the Universe’s Oldest Light

The cosmic microwave background, which is the faint afterglow left behind by the Big Bang, contains valuable information about the early universe. Recent observations suggest that the polarization of this ancient light may undergo a slight rotation. This effect is known as cosmic birefringence.

Scientists suspect that this subtle rotation could be linked to hypothetical elementary particles called axions. Precisely determining the amount of rotation, known as the birefringence angle, is therefore essential for testing possible new physics. Researchers measure this angle by analyzing the strength of a signal called the CMB EB correlation. Earlier studies estimated the rotation angle to be around 0.3 degrees.

Investigating the Measurement Uncertainty

The research team was led by University of Tokyo Graduate School of Science PhD candidate Fumihiro Naokawa, working with Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI) Project Associate Professor Toshiya Namikawa. Their analysis carefully examined the uncertainties that affect measurements of cosmic birefringence.

Their results suggest that the rotation angle may actually be larger than the previously reported value of about 0.3 degrees.

“Can you tell what day it is, just by looking at a clock? No, you cannot. To determine the date from the clock hands, you need to know how many times the hands have rotated since a specific reference date and time. In scientific terms, a situation like this clock’s hands — where observing only the current state does not reveal how many rotations occurred in the past — is described as having 360-degree phase ambiguity.

“Like a clock, the CMB we can observe is only in its current state. Therefore, rotation angles such as 0.3 degrees, 180.3 degrees, and 360.3 degrees should be indistinguishable. This means the birefringence angle has a phase ambiguity of 180 degrees,” said Naokawa.

Solving the Phase Ambiguity Problem

To address this issue, the researchers developed a technique to resolve the ambiguity. They discovered that the detailed shape of the EB correlation signal contains clues about how many times the polarization direction may have rotated.

By analyzing these subtle features within the EB correlation signal, scientists may be able to determine the true rotation angle and eliminate the ambiguity.

Improving Future Cosmology Experiments

The new method provides a tool for analyzing future high precision observations of cosmic birefringence. Upcoming experiments, including the Simons Observatory and LiteBIRD, could use this technique to test new theoretical models of fundamental physics.

The team also discovered that when this phase uncertainty is considered, cosmic birefringence influences another signal in the cosmic microwave background known as the EE correlation. Scientists use the EE correlation to estimate the Universe’s “optical depth,” an important quantity for studying cosmic reionization. Because of this connection, the new findings may require researchers to revisit previously reported optical depth measurements.

A New Way to Confirm Cosmic Birefringence

In a separate study also published in Physical Review Letters, Naokawa examined ways to reduce errors introduced by telescopes when measuring cosmic birefringence. He proposed a method to confirm the effect by observing particular astronomical sources, including radio galaxies powered by supermassive black holes.

These observations could provide another way to verify cosmic birefringence and may help scientists uncover deeper insights into the nature of dark energy.

A study led by chemists at the University of Bristol found that the smell associated with mummies is not simply the result of aging or decay. Instead, it reflects a complex blend of substances used during embalming, along with preserved fabrics and materials wrapped around the body. Together, these lingering chemical traces reveal how mummification methods changed and became more sophisticated over hundreds of years.

Lead author Dr. Wanyue Zhao, Research Associate in Organic Geochemistry at the University of Bristol, said: “The findings mark a significant step forward in improving our understanding of Egyptian history and the fascinating ritual of mummification. Our analysis of the associated scents has uncovered new insights into how the practice developed through the ages and became increasingly sophisticated.”

Analyzing the Air Around Ancient Remains

To investigate the source of mummy scents, researchers examined the air surrounding extremely small mummy fragments about the size of a peppercorn. This approach differs from traditional techniques, which often require dissolving samples in solvents and can damage delicate artifacts.

The team used a combination of advanced analytical tools including solid phase microextraction, gas chromatography, and high resolution mass spectrometry. These methods allowed them to capture gases inside small sealed containers and separate the different scent components known as Volatile Organic Compounds (VOCs) so they could be studied in detail.

The research, published in the Journal of Archaeological Science, analyzed 35 samples of balms and bandages from 19 mummies. These remains spanned more than 2,000 years of Egyptian history between 3200 BC and 395 AD. Across all samples, scientists identified 81 distinct VOCs that offer clues about the materials used during the embalming process and the time periods in which the mummies were prepared.

Chemical Clues Reveal Embalming Ingredients

Even when present in extremely small quantities, these chemical compounds helped researchers identify the substances used in preservation. They grouped the compounds into four main categories connected to specific embalming ingredients.

Fats and oils generated aromatic compounds and short chain fatty acids. Beeswax produced mono-carboxylic fatty acids and cinnamic compounds. Plant resins released aromatic compounds and sesquiterpenoids, while bitumen produced naphthenic compounds.

Dr. Zhao said: “Our findings showed the chemical patterns varied across historical periods. Earlier mummies had simpler profiles dominated by fats and oils, while later mummies displayed more complex mixtures incorporating imported resins and bitumen. Such materials were more costly and required more specialized preparation, as the practice became more advanced.”

Different Body Parts Used Different Embalming Recipes

The chemical signatures also varied depending on which part of the body was sampled.

“For instance, samples from heads often contained different patterns than those from torsos, suggesting embalmers applied distinct recipes to separate parts of the body to possibly aid preservation. This is an area which needs further analysis and research to better understand what techniques were used and why,” Dr. Zhao added.

The findings provide a more detailed understanding of known embalming mixtures and offer deeper insight into how these preservation techniques developed over time.

A New Way to Study Mummies Without Damaging Them

Study co-author Richard Evershed, Professor of Chemistry at the University of Bristol, said: “Our volatile analysis proved sensitive enough to detect residues at extremely low concentrations. For example, bitumen biomarkers were previously difficult to detect with earlier soluble residue methods.

“This approach expands the study of ancient Egyptian funerary practices, presenting a clearer, fuller picture of mummification recipes, material choices, and preservation strategies.”

The technique could also be valuable for museums and research collections. Sampling the air around mummies provides a fast, non destructive method for examining fragile remains while preserving their physical condition.

Study co-author Ian Bull, Professor of Analytical Chemistry at the University of Bristol, added: “Physical sampling still plays a role for detailed work, yet volatile analysis provides an effective and enlightening first step for studying embalmed remains across collections and time periods.”

Researchers led by a team at the Center for Advanced Systems Understanding (CASUS) at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) have now introduced a dependable and reproducible theoretical approach to tackle this problem. Their predictions were validated through measurements on real material samples. The team believes this advance could significantly accelerate research on polyheptazine imides and spark rapid growth in the field.

Carbon Nitride Materials and Visible Light Absorption

Polyheptazine imides belong to the broader class of carbon nitrides. These materials consist of layered structures that resemble graphene but are built from nitrogen rich ring shaped molecular units.

While graphene is known for exceptional electrical conductivity, it does not function well as a photocatalyst. Polyheptazine imides differ in a crucial way. Their electronic band gaps allow them to absorb visible light, which makes them suitable for sunlight driven chemical reactions.

Carbon nitride materials also offer several practical advantages. They are relatively inexpensive to produce, non toxic, and thermally stable. However, early versions of these materials did not perform well as photocatalysts because their internal properties limited effective charge separation.

When a photon strikes a material, it can excite an electron and move it away from its original position, leaving behind a positively charged hole. If the electron quickly recombines with the hole, the energy is released only as heat or light instead of driving chemical reactions.

“Polyheptazine imides containing positively charged metal ions exhibit markedly improved charge separation. This feature renders them highly suitable for practical applications,” says first author Dr. Zahra Hajiahmadi.

Computer Modeling Speeds the Search for Better Catalysts

Improved materials are needed to unlock the economic potential of several photocatalytic processes. These include water splitting (to produce hydrogen as a fuel), carbon dioxide reduction (to produce basic carbohydrates as fuels or industrial chemicals), and hydrogen peroxide production (as a basic industrial chemical).

Designing a polyheptazine imide catalyst that performs well for a specific reaction requires careful control over many aspects of its structure. Creating and testing every possible material candidate in the laboratory would be unrealistic. Computational methods therefore play an essential role in narrowing down the possibilities.

“The design space is enormous,” explains Prof. Thomas D. Kühne, Director of CASUS, head of the CASUS research team “Theory of Complex Systems” and senior author of the study. “One can for example add functional groups on the surface or substitute specific nitrogen or carbon atoms with oxygen or phosphorus atoms.”

Kühne’s research group is developing advanced numerical techniques designed to be both efficient and capable of accurately reproducing the chemical and physical behavior of complex materials.

Systematically Testing 53 Metal Ions

A defining feature of polyheptazine imides is the presence of negatively charged pores within the material. These pores can host positively charged metal ions, which can significantly enhance catalytic performance.

Hajiahmadi’s work represents the first comprehensive investigation of how different metal ions influence the optoelectronic properties of these materials. The study examined 53 metal ions in total, categorizing them according to where they sit within the structure (in plane or between layers) and how they alter the geometry of the material (resulting in a distortion or not).

“We used a reliable and reproducible computational framework that goes beyond conventional modeling approaches,” says Hajiahmadi. “Standard computational studies of photocatalysts typically focus on ground-state properties and neglect excited-state effects, despite the fact that photocatalysis is inherently driven by photoexcited charge carriers. Specifically, we employ many-body perturbation theory methods.”

These methods begin with a simplified model system that does not include particle interactions. Interactions are then added as small corrections, allowing researchers to approximate how large numbers of particles affect each other. Although such calculations require substantial computing power and are rarely applied in this field, the new study demonstrates their value. The framework provides an accurate description of how these materials absorb light and how their electronic structure behaves under illumination.

Experiments Confirm Theoretical Predictions

Using their computational approach, the researchers explored how different metal ions alter the structure of the polyheptazine imide network. Their analysis revealed that introducing ions can cause measurable structural changes, including shifts in the spacing between layers and modifications to local bonding environments. These structural variations directly influence the electronic band structure and optical properties of the materials, affecting how efficiently they capture light.

To test their predictions, the team synthesized eight polyheptazine imide materials, each incorporating a different metal ion. The materials were then evaluated for their ability to catalyze hydrogen peroxide production.

“The results clearly showed a high degree of agreement to our predictions and outperformed competing calculation methods,” Hajiahmadi concludes.

Kühne adds: “If there was some doubt about polyheptazine imides being one of the most promising platforms for next-generation photocatalytic technologies, I believe this work put them to rest. The path toward the targeted design of efficient polyheptazine imide photocatalysts for sustainable reactions is clearer now. I firmly believe that it will be taken often and successfully.”