On 18 November, Dr Betty Tijms and Prof. Pieter Jelle Visser published a paper in the Brain journal, in which they identify three different Alzheimer’s disease subtypes based on proteomics analyses of cerebrospinal fluid samples from participants in the EMIF-MBD and ADNI studies. The A/T/N classification for Alzheimer’s Disease (AD) defines AD based on the presence of amyloid plaques (A), tau tangles (T) or other neurodegeneration markers (N) in the brain. However, the clinical symptoms of AD vary considerably from individual to individual, with varying ages of onset and rates of disease progression. Cerebrospinal fluid (CSF) samples contain hundreds of different proteins, and analyses of these proteins using proteomics techniques might provide some clues and biological identifiers that better capture the clinical heterogeneity of AD.
To evaluate the proteomic profiles in people with AD and their non-affected counterparts, the researchers analysed CSF samples from participants enrolled in the EMIF-MBD and ADNI clinical studies. In both cohorts, the proteomic profiles of CSF from participants with AD differed substantially from those of people without AD. Looking more closely at the CSF proteins that were present at increased or decreased levels, and analyzing the biological processes associated with these proteins, the researchers identified three separate AD subtypes present across the two studies. The first was defined as a “hyperplastic” subtype, characterized by higher levels of neuronal injury, while the second subtype showed higher levels of innate immune activation, and greater brain atrophy on MRI scans. This subtype also appeared to show faster clinical progression of AD, with steeper worsening over time based on the CDR-SB cognitive test scale. The third subtype of AD was associated with increased markers of blood-brain-barrier dysfunction and greater levels of vascular damage on MRI scans.
https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awaa325/5986603#212827688
