Distinct Alzheimer Disease Subtypes Using Proteomic Fingerprints: Fiona Elwood, PhD

WATCH TIME: 4 minutes

"It was really interesting to see that there was this subtype where actually it was enriched for changes in the blood-brain barrier. The protein signature was enriched for changes in blood-brain barrier… if you’ve got a leaky blood-brain barrier, you could see more of those albumin proteins in the CSF."

Due to the advancements in understanding of Alzheimer disease (AD) and its pathology, precision medicine has become more of a realistic possibility. In recent years, clinicians have begun to characterized patients based on their biological makeup instead of clinical symptoms. To further characterize the molecular processes that drive disease progression and to correctly stage those processes along the disease trajectory, Johnson & Johnson brought together large biofluids proteomic datasets from different neurodegenerative disease cohorts.

At the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 1, in Philadelphia, Pennsylvania, analyses of CSF proteomics data from the Spanish ACE Alzheimer’s disease cohort (n = 1321) were presented. These data provided an independent validation of previously conducted research that identified 3 different AD subtypes. These subtypes were characterized by elevated levels of proteins associated with either (1) neuronal plasticity, (2) innate immunity, or (3) blood-brain barrier dysfunction.

Following the meeting, NeurologyLive^® sat down with Fiona Elwood, PhD, disease area stronghold leader in neurodegeneration at Johnson & Johnson, who discussed the 3 subtypes in greater detail. She spoke on the innate immune subtype, and how it involves synaptic dysfunction and microglial activity, linking inflammation to AD progression. Elwood noted that the second subtype, marked by blood-brain barrier dysfunction, is particularly interesting due to the common comorbidity of vascular pathology in patients with AD. Overall, she described how these data emphasize the importance of subtyping AD to target therapeutic approaches more effectively and drive future research.

REFERENCES
1. Smets B, Khan A, Greene J, et al. Large-scale proteomics to enable precision medicine for Alzheimer disease. Presented at: Alzheimer’s Association International Conference; July 28-August 1, 2024; Philadelphia, PA.
2. Gargas T, Hou L, Wrzesinski T, et al. Identification of cross-diagnostic protein signatures and subtypes of neurodegenerative diseases using multi-task deep learning on the UK