On 9 January, EPND partners from Amsterdam UMC and Maastricht University published new findings in the Nature Aging journal, identifying five molecular subtypes of Alzheimer’s disease. These findings, which are based on biomarker analyses of cerebrospinal fluid samples, shine a light on the biological heterogeneity of Alzheimer’s disease, and the potential need for tailored treatment to optimise patient outcomes.

Read on to learn more!

Amyloid and tau are often cited as culprit proteins in Alzheimer’s disease (AD), forming aggregates that damage neurons and impair cognition. However, there are many disease drivers of AD beyond amyloid and tau, spanning processes from neuroinflammation to vascular dysfunction and RNA dysregulation.

In their Nature Aging paper, EPND partners Pieter Jelle Visser, Betty Tijms and Charlotte Teunissen used advanced analytical techniques to probe the composition of cerebrospinal fluid (CSF) samples from 419 people with AD, comparing them to samples from 187 people who don’t have AD. Individuals were selected from a number of Amsterdam UMC cohorts in the EPND Catalogue, including the EMIF-AD and EPAD studies. By examining 1058 proteins found in CSF samples from people with AD, they were able to identify five biological variants within this group, each with defined molecular characteristics. For example, the first variant was characterised by increased amyloid production, while a second subtype showed disruption of the blood-brain barrier, and reduced amyloid production.

The research team also expanded their analysis to genetic and clinical characteristics, showing that changes in CSF samples in different subgroups may also be associated with distinct genetic risk profiles, and clinical characteristics. For instance, the 137 individuals in subtype 1 had the longest average survival time (approximately 8.9 years), with over-representation of a TREM2 risk variant. While the 56 individuals in subtype 5 showed evidence of blood-brain barrier dysfunction, and a higher risk of progression from MCI to dementia.

These findings have potential implications for therapy, as people from different subtypes may respond more or less well to different types of treatment. They also demonstrate the value of sharing biosamples and data, which came from five different cohorts, and allowed the research team to characterise the molecular heterogeneity of AD in a highly detailed way.

Congratulations to the authors!

Read the original article, here: https://www.nature.com/articles/s43587-023-00550-7