A lay summary written by Natalie Pye & reviewed by Dr Ryan West
Background
Alzheimer’s disease affects people differently, with symptoms and speed of disease progression differing between people living with the condition. Some changes in the brain related to Alzheimer’s occur years before any symptoms show. As more parts of the brain become damaged, symptoms such as memory loss and difficulties with language present, commonly known as dementia.
Why is the study important?
To determine if a person has Alzheimer’s and estimate the time of dementia onset more accurately, biological markers (biomarkers) to track early disease-causing changes in the brain are needed. This could provide scientists with the improved ability to predict decline in brain function and indicate potential therapeutic targets, to halt the disease before it progresses to dementia.
What did the authors do and how did they do it?
Over 3 years the authors measured changes in the levels of 5 candidate biomarkers in the cerebrospinal fluid (a fluid found around the brain & spinal cord) of 111 participants with symptoms of decline in brain function but no diagnosis of dementia and 76 participants without any symptoms.
They analysed how the changes in levels of these candidate biomarkers over time might relate to Alzheimer’s development by comparing the rate of biomarker level change in participants with symptoms and participants without symptoms.
The relationship between candidate biomarker changes and brain function was also tested, using a series of questions and tests for memory, language, and logic, such as repeating a phrase back to the examiner or following a verbal command.
What are the results?
Interestingly, out of the 5 candidate biomarkers tested, the levels of 1 potential biomarker NPTX2, showed the most significant changes over the 3 years. NPTX2 is a protein in the brain important for allowing neurones to send signals and communicate.
The level of NPTX2 decreased more over time in the symptomatic participants than participants without symptoms. There was a larger decrease in participants who were positive for a known Alzheimer’s biomarker and participants whose diagnosis worsened during the experiment – essentially participants whose disease has progressed further.
Decline in NPTX2 levels correlated with decline in brain function, especially in symptomatic and Alzheimer biomarker positive participants. This correlation was also seen in participants without symptoms, suggesting NPTX2 may be a predictor of brain dysfunction prior to Alzheimer’s onset.
What do the finding mean going forward for people with the disease?
Development of a test to easily detect changes in NPTX2 would allow for earlier and more accurate predication of Alzheimer’s onset and progression to dementia. NPTX2 could also be explored as a therapeutic target, although this needs more work to be conclusive.