On 9 January, a team of researchers at Amsterdam University Medical Center published new findings in the Nature Aging journal, identifying five molecular subtypes of Alzheimer’s disease. These findings, which are based on 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.
Amyloid and tau are often cited as culprit proteins in Alzheimer’s disease (AD), forming plaques and tangles that damage brain cells and prevent normal functioning. However, there are many biological processes and drivers of AD, such as inflammation or problems affecting blood vessels. In their Nature Aging paper, Pieter Jelle Visser and Betty Tijms use advanced analytical techniques to probe the composition of cerebrospinal fluid (CSF) samples from 419 people with AD, compared to people who don’t have AD. By examining 1058 proteins found in CSF samples from people with AD, they show that there are five biological variants within this group, each with defined molecular characteristics. For example, the first variant is characterised by increased amyloid production, while a second subtype shows 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.
