Exosomes
Researchers at Aarhus University in Denmark have identified a defect in the production of exosomes within cells, linked to a mutation found in patients with dementia. Their findings are published in the journal of the Alzheimer’s Association, *Alzheimer’s & Dementia*.
Advocates of Intelligent Design argue that all genetic information must originate from an intelligent agent, claiming that anything both complex and specified cannot arise without deliberate design. Their proposed designer is invariably indistinguishable from the god of the Bible and Qur’an: an all-knowing, all-powerful and supposedly benevolent creator.
What they never address is why a system attributed to such a being should fail at all—let alone in ways that cause profound suffering. It is akin to a human engineer producing an aircraft with engines that randomly fail or wings that detach mid-flight. And because this designer is held to be omniscient, the failure cannot be inadvertent. It must have been foreseen and deliberately incorporated, making such mutations part of the intended plan rather than unfortunate accidents.
Following the internal logic of ID creationism, Alzheimer’s dementia would therefore count as an intended outcome—meeting William Dembski’s own criteria for “complex specified genetic information”. This provides yet another instance, alongside the cancer example I discussed recently, of biological processes that appear designed to destroy. It sits comfortably among the many parasites and pathogens explored in The Malevolent Designer: Why Nature’s God is Not Good, all pointing to a distinctly malign pattern in the supposed “design”.
ID proponents typically fall back on blaming “The Fall”, implying the existence of another creative force beyond the control of their designer. This manoeuvre only further undermines their claim that ID is a scientific enterprise rather than creationism thinly disguised, since it relies on biblical literalism to rescue the argument from the conclusion of an incompetent or malevolent designer—an outcome that is theologically awkward and, for many believers, outright heretical.
What are exosomes? Exosomes are tiny, membrane-bound vesicles released by almost all cell types. They are part of the broader family of *extracellular vesicles* and typically measure around 30–150 nanometres in diameter—far smaller than most other cellular structures.The Aarhus research is summarised in an Aarhus Universitet Faculty of Medicine news item by Vibe Bregendahl Noordeloos.
How exosomes are formed
They originate inside the cell. As parts of the cell membrane fold inward, they form small internal vesicles within larger compartments called multivesicular bodies. When these multivesicular bodies fuse with the cell’s outer membrane, the internal vesicles are released into the surrounding environment as exosomes.
Their core functions
Exosomes are essential for communication between cells. Their key roles include:
- Transporting molecular cargo
They carry proteins, lipids, mRNA, microRNA, and other biomolecules. This cargo can influence the behaviour of recipient cells, effectively acting as biological “messages”.- Regulating immune responses
They help activate or suppress immune cells, depending on context. Some pathogens even hijack exosomes to evade immunity.- Supporting tissue maintenance and repair
Exosomes can deliver signals that promote cell growth, differentiation, or wound healing.- Removing unwanted material
Cells use exosomes to export damaged proteins, metabolic waste, and misfolded molecules—effectively a controlled disposal route.
Why they matter in diseases such as Alzheimer’s
Because exosomes move material between cells, any defect in their formation or release can disrupt cell-to-cell communication. In neurodegenerative diseases, exosomes are thought to play a double role:
- Faulty exosome production may impair normal neuron maintenance.
- Conversely, exosomes can also spread harmful proteins such as tau or beta-amyloid.
Thus, a mutation that compromises exosome production or quality can contribute to the gradual collapse of neural networks seen in dementia.
Researchers discover cell defect linked to the development of Alzheimer’s
They’re tiny particles – with potentially huge human consequences. Researchers from Aarhus University have identified a defect in the production of so-called exosomes in cells, associated with a mutation seen in dementia patients. This could lead to a better understanding of the development – and perhaps even a treatment – of Alzheimer’s.
Exosomes are the epitome of microscopic. So small that just the tip of a grain of rice equals millions of them. Nevertheless, new research from the Department of Biomedicine at Aarhus University shows that they may play a key role in the development of Alzheimer’s. Assistant Professor Kristian Juul-Madsen is one of the researchers behind a new study recently published in the scientific journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
Exosomes are used to communicate with and activate surrounding cells, and we have now identified a defect in both the production and the quality of exosomes in cells that we know are predisposed to Alzheimer’s.
Assistant Professor Kristian Juul-Madsen, first author
Department of Biomedicine
Aarhus University
Aarhus, Denmark.
To date, four main genes have been identified that can be linked to the inherited form Alzheimer’s. And to understand the new research findings, we need to dive a bit into the technical explanations. One of these four genes is called Sorl1. This gene encodes the protein SORLA. And when the SORLA-protein mutates, there is a risk of developing Alzheimer’s. What Kristian Juul-Madsen and his research colleagues have now discovered is that if the SORLA-protein is defective, the brain cells become significantly worse at producing exosomes.
We found that cells with this mutation produced 30% fewer exosomes, and those that were produced were significantly worse at stimulating the growth and maturation of surrounding cells – in fact, up to 50% less effective than in cells where the SORLA-protein is not mutated.
Assistant Professor Kristian Juul-Madsen.
And this could be crucial for future Alzheimer’s research, he says.
It tells us that exosomes produced particularly by the brain’s immune cells play an important role in maintaining brain health – and that mutations leading to fewer and poorer quality exosomes are associated with increased risk of Alzheimer’s.
Assistant Professor Kristian Juul-Madsen.
Kristian Juul-Madsen hopes that the research findings may eventually lead to improved treatment of Alzheimer’s.The potential is very clear. We now have the opportunity to investigate new treatments for Alzheimer’s – either by stimulating the function of SORLA so that the cells produce more and better exosomes, or by targeting other known receptors that can enhance exosome production.
Assistant Professor Kristian Juul-Madsen.
Alzheimer’s is the most common form of age-related dementia in Denmark. It is estimated that around 55,000 Danes are affected, and there is currently no treatment for the disease.
Publication:
For anyone committed to Intelligent Design, findings like these ought to trigger some uncomfortable questions. A system as central as exosome production—responsible for cellular communication, waste management and overall homeostasis—should not be prone to catastrophic breakdown if it were the product of a competent, foresighted designer. Yet here we have a mechanism so fragile that a single mutation derails it, contributing to one of the most devastating neurodegenerative diseases known.Abstract1 BACKGROUND
INTRODUCTION
Mutations in SORL1, encoding the sorting receptor Sortilin-related receptor with A-type repeats (SORLA), are found in individuals with Alzheimer's disease (AD). We studied SORLAN1358S, carrying a mutation in its ligand binding domain, to learn more about receptor functions relevant for human brain health.
METHODS
We investigated consequences of SORLAN1358S expression in induced pluripotent stem cell (iPSC)-derived human neurons and microglia, using unbiased proteome screens and functional cell assays.
RESULTS
We identified alterations in the SORLAN1358S interactome linked to biogenesis of exosomes. Consequently, the mutant receptor failed to promote release and neurotrophic qualities of exosomes, a defect attributed to altered exosomal content of microRNAs controlling neuronal maturation.
DISCUSSION
We identified a role for SORLA in controlling quantity and neurotrophic quality of exosomes secreted by cells, suggesting impaired cellular cross talk through exosomes as a pathological trait contributing to AD pathology in carriers of SORL1 variants.
Highlights
- Familial Alzheimer's disease mutation in SORL1 changes interactome of mutant Sortilin-related receptor with A-type repeats (SORLA).
- Mutant SORLA impairs release of exosomes from neurons and microglia.
- Mutant exosomes lack neurotrophic qualities.
- Defect linked to alterations in microRNA content.
Sortilin-related receptor with A-type repeats (SORLA) is a 230 kDa type-1 transmembrane protein expressed in various mammalian cell types, including neurons and microglia in the human brain (reviewed in1, 2). SORLA acts as an intracellular sorting receptor directing multiple target proteins between Golgi, cell surface, and endo-lysosomal compartments, sorting paths central to endocytic and secretory functions of cells. SORLA is best known for its ability to act as neuronal sorting receptor for the amyloid precursor protein (APP), preventing its proteolytic breakdown into amyloid-β peptides (Aβ), a causative agent in Alzheimer's disease (AD).3-6 Intriguingly, genetic studies have identified the encoding gene SORL1 as a novel disease gene in familial forms of AD (FAD). In fact, SORL1 variants predicted in silico as damaging to protein structure may be present in as many as 3% of all patients with FAD of unknow etiology.7-9 This prediction is supported by studies in cultured cells, documenting impaired folding and maturation of the receptor polypeptide seen with many SORL1 gene variants.10 A second class of SORL1 variants, associated with AD thus far, exhibit disrupted intracellular sorting of the receptor and its target APP, corroborating control of amyloidogenic processing of APP as a receptor function of disease relevance.10-13 Still, whether association with FAD is solely explained by the ability of SORLA to sort APP in neurons, or whether yet unknown receptor functions contribute to the risk of the disease seen with some SORL1 alleles, remains an open question. In line with this notion, prior analysis of mutation G511R in the extracellular domain of the receptor identified binding of Aβ to this domain as another function of SORLA lost in FAD.14
Conceptually, the unbiased study of loss-of-function variants in SORL1 associated with FAD may enable us to uncover novel receptor interactions crucial to aging brain health not constrained by prior hypotheses of receptor actions. Here, we focused on the functional characterization of the mutation N1358S as it localizes to the complement-type repeats, a major ligand binding domain in the receptor polypeptide. Combining unbiased interactome studies with targeted analyses of induced pluripotent stem cell (iPSC)-derived human brain cell types, we identified impaired biogenesis and loss of neurotrophic actions of exosomes as cellular phenotypes caused by expression of SORLAN1358S. These findings document a novel role for SORLA in cell-to-cell communication through exosomes, and suggest defects in these processes to contribute to AD pathology in carriers of the SORL1N1358S variant.
Juul-Madsen K, Rudolph I-M, Gomes JP, et al.
Familial Alzheimer's disease mutation identifies novel role of SORLA in release of neurotrophic exosomes.
Alzheimer's Dement. 2025; 21: e70591. https://doi.org/10.1002/alz.70591
Copyright: © 2025 Alzheimer's Association®.
Published by John Wiley & Sons, Inc. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
If ID advocates genuinely engaged with the implications, they would be forced to confront a stark choice. Either their designer constructed a communication system so poorly engineered that it fails predictably and repeatedly across human populations, or the resulting suffering is intentional. Both conclusions sit uneasily with their claims of omniscience, benevolence and flawless design.
Instead, the pattern is simply ignored. The complexity of the system is seized upon as evidence of design, while its failures—equally complex and far more consequential—are dismissed as theological inconveniences. Yet the science offers no refuge for such evasions. The mutation exists; the defect exists; the disease exists. If one insists on attributing these to a designer, then that designer must bear responsibility for the outcome. That is the inescapable logic ID proponents avoid, and every new discovery of a biological failure pushes the contradiction further into view.
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