Growing older brings many health concerns, and among them, memory loss linked to dementia is a pressing issue. With the number of people affected expected to grow steeply in the coming years, scientists are working hard to find early clues that could help identify the condition sooner. A recent investigation highlights how certain changes in spinal fluid, the clear liquid that surrounds and cushions the brain and spinal cord, may signal the early development of dementia.

Clinical scientists led by Professor Rüdiger Seitz at Heinrich-Heine-University Düsseldorf looked closely at this connection. Their work at the LVR-Klinikum Düsseldorf combined fluid testing with mental exercises designed to measure memory and thinking skills, often referred to in clinical settings as neuropsychological assessments. The results were published in the respected medical journals Neurological Research and Practice and Journal of Clinical Medicine.

Nearly two hundred individuals who showed signs of dementia took part in the study. They were split into two groups depending on how long their symptoms had lasted. One clear finding stood out: among those who had noticed changes more recently, lower amounts of a substance known as amyloid beta 1-42, a protein linked to Alzheimer’s disease and referred to here as sticky brain protein, in their spinal fluid went hand in hand with lower scores on memory tests. Those with higher levels of this protein generally performed better on these tests (red area in figure). These differences were not as clear in people who had been living with symptoms for a longer period (blue area in figure). In a group of dementia patients diagnosed to suffer from normal pressure hydrocephalus a low amyloid beta 1-42 protein signified, in addition to memory impairment, also progressive  gait problems and urine incontinence.

“Our results substantiate the relevance of sticky brain protein for memory deficits and support the amyloid cascade hypothesis for Alzheimer’s dementia,” Professor Seitz  said. The amyloid cascade hypothesis is a widely supported idea that suggests Alzheimer’s begins when amyloid proteins build up in the brain, leading to damage. Professor Seitz also noted that other markers found in spinal fluid, such as phosphorylated tau protein, which is a sign of damage inside nerve cells, and the ratio between different forms of amyloid beta, showed some connection to thinking difficulties. However, none were as closely tied to memory issues as sticky brain protein. Other substances tested, such as total tau protein, neuron-specific enolase, a molecule that appears when nerve cells are injured, and protein S100B, which is linked to inflammation in the brain, did not show useful patterns.

Recognizing these patterns is important for doctors. If sticky brain protein can point to memory issues early, then it could become a helpful tool to detect dementia before it worsens. Professor Seitz’s team also found that skills related to understanding space and shapes, which are also affected by dementia, did not show the same strong connection to this protein. That means memory and visual thinking might be affected by different processes in the brain.

Timing is key. Testing for sticky brain protein early on, especially within months of first noticing memory trouble, showed the clearest results. This supports the view that biological changes inside the brain begin before major memory loss appears. “This pattern aligns with the idea that neurodegenerative processes are most dynamic before cognitive symptoms manifest,” Professor Seitz concluded. Neurodegenerative processes refer to the slow breakdown and eventual loss of nerve cells in the brain.

Understanding how markers in blood or spinal fluid connect to thinking and memory helps build a clearer picture of how dementia develops. Finding this link suggests that sticky brain protein might help in spotting dementia earlier. “Since the strongest associations were found in the early stages of the disease, this is also good news for putative treatments in dementia” Professor Seitz pointed out, highlighting how changes in this target protein may affect trouble with recalling words and recognizing them later. As medical research continues to explore the changes behind Alzheimer’s, studies like Professor Seitz and colleagues’ contribute to developing better ways to detect and potentially treat the disease earlier and more effectively.

Journal References

Klemke L.L., Müller-Schmitz K., Kolman A., Seitz R.J. “Evolution of Neurodegeneration in Patients with Normal Pressure Hydrocephalus: A Monocentric Follow up Study.” Neurological Research and Practice, 2023; 5:52. DOI: https://doi.org/10.1186/s42466-023-00272-6

Römer M., Lange-Asschenfeldt C., Müller-Schmitz K., Seitz R.J. “Cerebrospinal Fluid Biomarkers and Neuropsychological Abnormalities in Dementia: A Monocentric Study of Consecutive Patients.” Journal of Clinical Medicine, 2025; 14:710. DOI: https://doi.org/10.3390/jcm14030710