Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease in which the nerve cells that control the body’s muscles break down. Its course varies widely. Some patients deteriorate rapidly, while others live with the disease considerably longer, which makes it hard to predict early on how it will develop. Other pathological changes are known to occur in the brain in ALS, but until now it has been unclear how they affect progression. In a collaboration between Sweden, Japan and Italy, researchers examined how Alzheimer-related changes affect prognosis in ALS.

“Lund University conducts leading research into Alzheimer’s disease, while Nagoya University has a strong ALS research program. As I am a doctoral student at both universities, the idea arose to bring the two fields of research together in this study,” says Kazuki Obara, who is also a neurologist in Japan.

The researchers analyzed cerebrospinal fluid levels of amyloid beta, a biomarker for Alzheimer-related changes, in Japanese patient cohorts. The study included 264 ALS patients, 60% of them men and 40% women, with a mean age of 67 years. The control group consisted of 164 patients with other neurological diseases.

“We found that around 14 per cent of the patients with ALS showed signs of changes that also occur in Alzheimer’s disease,” Obara says.

The researchers also studied neurofilament light chain (NfL), a biomarker used in ALS to measure nerve cell damage. In patients with amyloid beta-positive changes, the link between high NfL levels and shorter survival was stronger than in patients without such changes. Data from another 153 ALS patients in Bologna, Italy, supported the findings. The researchers also observed an interaction between amyloid beta and NfL in how everyday physical function declined over time.

“The findings suggest that the same NfL level may have different prognostic significance depending on what other changes are present in the brain. One possible explanation is that several disease processes together make the nervous system more vulnerable, but the underlying mechanisms have not yet been established,” says Niklas Mattsson-Carlgren, researcher at Lund University and consultant neurologist at Skåne University Hospital.

The team also tested machine-learning models that combined NfL with other biomarkers, including amyloid beta. The models improved the identification of ALS, including in people whose NfL values fell within a grey area. In the future, NfL could be used in an initial assessment, followed by further biomarker analyses and a more detailed clinical examination when results are unclear.

“A more detailed prognosis may also be valuable in clinical trials. If participants with very different expected disease courses are included in the same study, it becomes more difficult to determine whether a treatment has an effect. Biomarkers may therefore contribute to better patient stratification and more efficient studies of new treatments,” says Mattsson-Carlgren.

Because the study is based on observational data, the results cannot yet guide clinical decisions, and the methods need to be confirmed in additional, independent patient groups. The researchers are now investigating whether biomarkers linked to other neurodegenerative diseases, such as Parkinson’s disease, also affect ALS prognosis. An ALS cohort is also being set up within BioFINDER, Lund University’s large research program on neurodegenerative diseases. Patients at the neurology clinics in Lund and Malmö will be invited to take part.

The study was carried out within a joint doctoral program between Lund University and Nagoya University and is published in eBioMedicine, part of The Lancet Discovery Science.

Source: Lund University, 20 October 2026. Publication: Obara K. et al., “Cerebrospinal fluid amyloid and neurodegeneration biomarkers in the diagnosis and prognosis of amyotrophic lateral sclerosis: A multicohort observational study”, eBioMedicine, 2026 – read the article