Aims

It is of great importance to get a better understanding of the heterogeneity within Alzheimer’s disease (AD). Here, we want to give an update on where we stand today, present new findings and give some future directions.

Methods

We have recently performed a review and meta-analysis summarizing the findings to date [1]. Our conclusions based on where we stand today were: 1) We need a framework that will aid with hypothesis formation, study design, interpretation of results, and understanding mechanisms in future subtype studies 2) To separate distinct subtypes of disease from disease staging, longitudinal information needs to be incorporated in models. 3) There is a need to harmonize subtyping methods across studies to increase generalizability and to compare results reliably.

Results

Our framework looks at the heterogeneity in AD along the two axis, typicality and severity. Individual subjects are positioned within this two-dimensional space in relation to risk factors, protective factors, and concomitant non-AD brain pathologies. Longitudinal subtyping data are presented and results from studies comparing subtyping methods.

Conclusions

To get a better understanding of the complexity and heterogeneity in AD will result in more personalized medicine in the future and opportunities for successful drug trials so we can finally find treatment approaches for such a complex and multifaceted disease like AD.

1. Ferreira, D., A. Nordberg, and E. Westman, Biological subtypes of Alzheimer disease: A systematic review and meta-analysis. Neurology, 2020. 94(10): p. 436-448.