New biomarker test accurately detects brain inflammation in Alzheimer’s and Parkinson’s

Scientists, led by Dr Evgeniia Lobanova and Prof Sir David Klenerman (UK DRI at Cambridge), have developed a biomarker to measure inflammation in the brain in Alzheimer’s and Parkinson’s. The research, published in Nature Communications, could improve early detection of the conditions and help to test new therapies in clinical trials. 

What was the challenge? 

As well as the hallmark build-up of proteins in Alzheimer’s and Parkinson’s, both diseases are also characterised by inflammation in the brain, which is seen to occur before the onset of clinical symptoms. 

Developing ways to accurately detect and measure inflammation has the potential to improve early diagnosis. It could also be used to monitor participants in trials for immunotherapy drugs, such as lecanemab (Leqembi) and donanemab (Kisunla), which have inflammatory side effects. 

What did the team do and what did they find? 

In this study, the researchers set out to establish whether measuring levels of a protein known as ASC (Apoptosis‐associated speck‐like protein containing a caspase recruit domain) could be a useful marker of inflammation in the brain. When activated, individual ASC proteins come together into a large complex called the ‘speck’. 

The researchers studied samples from people with Alzheimer’s and Parkinson’s, as well as healthy individuals, using advanced imaging techniques. They found that the number and shape of ASC specks in the blood of patients with early-stage Alzheimer’s and Parkinson’s were different from those in healthy individuals. These changes in the blood mirrored what they observed in spinal fluid samples.

In addition to ASC specks, the team also measured protein clumps commonly associated with these diseases, like amyloid-beta (linked to Alzheimer’s), p-tau (a marker of Alzheimer’s damage), and α-synuclein (connected to Parkinson’s). They created a new biomarker test using a combination of these markers, which could distinguish between healthy individuals and people with early-stage Alzheimer’s or Parkinson’s with very high accuracy.

What is the impact? 

This breakthrough suggests that measuring ASC specks and other protein markers in blood could become a convenient and reliable way to diagnose these diseases early and monitor inflammation during treatment. This could improve diagnostics and help test new therapies in clinical trials.

Prof Klenerman explained: 

"Our study presents a sensitive and specific method of measuring an inflammatory marker in the brain, and we have shown that this can be used to detect early-stage Alzheimer’s and Parkinson’s. By unlocking the potential of blood-based biomarkers like ASC specks, we can bring early and accurate diagnosis of these conditions within reach, paving the way for more effective treatments."

Dr Lobanova added:

“Next, we’ll be exploring whether the ASC speck biomarker can be used to monitor the effectiveness of drugs that block inflammatory pathways in neurodegenerative diseases. We will compare how ASC specks form in different models of Alzheimer’s and Parkinson’s, to try to better understand the underlying mechanisms of these conditions. We will also look at how the biomarker changes in people with Parkinson’s and Alzheimer’s as their disease progresses.”

Reference: Lobanova, E., Zhang, Y.P., Emin, D. et al. ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases. Nat Commun 15, 9690 (2024). https://doi.org/10.1038/s41467-024-53547-0