![[Adobe Stock]](https://sp-ao.shortpixel.ai/client/to_webp,q_glossy,ret_img,w_750,h_375/https://www.psypost.org/wp-content/uploads/2025/10/neurons-1-750x375.jpg)
A recent study indicates that microscopic, lipid-bound particles originating from the brain carry distinct genetic signatures depending on the type of dementia a person has. By analyzing these tiny packages, researchers identified specific regulatory molecules that differ between Alzheimer’s disease and various forms of frontotemporal dementia. These findings, published in Brain Communications, suggest a potential new avenue for early and accurate diagnosis of neurodegenerative conditions.
Dementia is an umbrella term for conditions characterized by memory loss and cognitive decline, affecting millions of people worldwide. Alzheimer’s disease is the most common cause, followed by frontotemporal dementia, which typically strikes at a younger age. In their early stages, these two diseases often share overlapping symptoms, making it difficult for doctors to tell them apart clinically.
Accurate diagnosis is a pressing need because new therapeutic drugs are entering the market. “New treatments for dementia can only help patients if we can accurately diagnose the type of dementia early, with misdiagnosis impacting the success of patient treatment and the ability to test new drugs in clinical trials,” Gemma Lace, associate dean and researcher at the University of Salford’s School of Science, Engineering & Environment, told PsyPost.
To find early biological markers, scientists are looking at small extracellular vesicles, which are tiny, lipid-bound bubbles released by cells to communicate with one another. “Small extracellular vesicles (sEVs) are fascinating structures that have only quite recently been implicated in neurodegenerative diseases, in particular, in the brain regional ‘spread’ of pathogenesis,” Lace said.
“Most studies have not explored brain sEV cargoes given the challenges associated with tissue access, yet the brain is the primary site of damage in dementia,” Lace added. “We were curious to know whether sEV cargoes varied between different sub-types of dementia given the research understanding around differential disease pathways, and if this variation could shed further light on disease process and/or have diagnostic value.”
Because these microscopic packages can cross the blood-brain barrier and enter the bloodstream, they offer a window into what is happening inside the brain. Past work has shown that looking at bodily fluids can yield clues about brain health; for example, a study covered by PsyPost in 2026 found that blood tests could accurately identify Alzheimer’s disease and frontotemporal dementia by looking at disease-linked proteins.
Inside these vesicles, cells pack various types of cargo, including microRNAs. MicroRNAs are short strands of genetic material that help control how genes are expressed, often by turning certain genetic instructions off. Previous research provides evidence that these molecules play a role in brain diseases. A study covered by PsyPost in 2024 demonstrated that specific microRNAs are altered in both the blood and brain tissue of those with Alzheimer’s pathology.
In neurodegenerative diseases, toxic proteins build up in the brain. Normally, the body uses cellular recycling systems, known as autophagy, to clear away these toxic accumulations. The authors of the new study suspected that different forms of dementia might involve unique disruptions to these recycling pathways. By examining the microRNA packed into brain-derived vesicles, they aimed to see if they could differentiate Alzheimer’s disease from frontotemporal dementia and its specific genetic variants.
The research, led by Joseph Morgan of the University of Salford, utilized post-mortem brain tissue from the frontal lobes of 25 individuals. The sample included five people who had Alzheimer’s disease, fifteen people with different genetic mutations that cause frontotemporal dementia, and five older adults without any clinical dementia diagnosis. For the molecular tests, the researchers analyzed a subset of three samples from each diagnostic group.
First, the research team isolated the small extracellular vesicles directly from the frozen brain tissue. They then chemically treated the samples to strip away any genetic material stuck to the outside of the bubbles, ensuring they were only measuring the cargo safely sealed inside. After extracting the microRNAs, the scientists used a laboratory technique that amplifies genetic material to measure the levels of seven specific microRNAs known to regulate cellular recycling.
The researchers found distinct differences between the groups. A microRNA called miR-224-5p was detected at much higher levels in the vesicles of individuals with Alzheimer’s disease and those with a specific tau-related mutation for frontotemporal dementia. Specifically, this molecule showed an absolute fold increase of over 4 times in Alzheimer’s samples and over 7 times in the tau-mutation samples, compared to the healthy brains.
Another target, miR-106a-3p, was elevated in the Alzheimer’s disease samples compared to the control group and all the frontotemporal dementia subgroups. After the scientists applied strict statistical adjustments to account for multiple comparisons, however, these specific group-to-group differences for miR-106a-3p were not statistically significant.
To get a broader picture, the team also mapped the entire microRNA landscape of the vesicles using genetic sequencing. This exploratory analysis identified unique panels of altered microRNAs for each disease type. For instance, a molecule named miR-26a-2-3p was elevated in Alzheimer’s disease samples when compared to the healthy controls. It was also elevated in the Alzheimer’s samples when compared directly to all three genetic forms of frontotemporal dementia.
“Our study has identified that different subtypes of dementia, that have similar symptoms, have different biological fingerprints within tiny brain vesicles,” Lace noted. “This is very exciting with respect to developing new methods of early and accurate diagnosis.”
As with all research, there are some caveats to consider. “This was a relatively small study given post-mortem human brain tissue is challenging to secure, with sample volumes available being limited,” Lace explained. “This meant we had to be very selective around the experiments we need to get the most meaningful data, and there were many things we were unable to explore due to the amount of tissue available to us.”
Because the sample sizes were small, there is an increased chance of missing subtle but real biological differences. The healthy control group was also older on average than the individuals in the disease groups, introducing an age difference that could potentially influence the types of microRNA found in the brain.
The results provide a snapshot of the brain after death, meaning post-mortem tissue degradation could have affected the stability of the genetic material. Furthermore, the exact microRNA signatures found directly in brain tissue may not perfectly match what is floating in a patient’s bloodstream or saliva. The brain is highly complex and made up of diverse, non-uniform tissue and cell types, so a sample from the frontal lobe may not represent the entire organ.
Future research will need to validate these candidate markers in much larger groups of patients, and scientists plan to test whether these same microRNA signatures can be reliably detected in more easily accessible bodily fluids. “It would be great to explore whether these brain sEV biomarker variations are detectable in peripheral tissues such as blood which is an accessible fluid for diagnostic use,” Lace said.
The study, “Distinct brain extracellular vesicle microRNA profiles differ in frontotemporal dementia and Alzheimer’s disease,” was authored by Joseph Morgan, Toby Aarons, Arijit Mukhopadhyay, and Gemma Lace.