Personalized treatment for Alzheimer’s disease based on molecular subtypes
Alzheimer’s disease (AD) is the most common cause of dementia. It is pathologically defined by amyloid plaques and tau tangles in the brain. The underlying pathophysiology of AD is, however, heterogeneous, and this hampers the search for a cure. Recently, I discovered three distinct molecular AD subtypes using cerebrospinal fluid (CSF) proteomics (Tijms et al., 2020, Brain). These subtypes showed distinct underlying pathways: one subtype was characterised by inflammation, another showed disrupted blood-brain barrier function and the third showed abnormal amyloid metabolism. This means that each subtype probably requires specific treatment.
My goal is to advance personalized treatments in AD by tailoring treatments to a patient’s molecular subtype. As a first step towards this goal, I aim to write two papers on analyses I have already largely performed:
1. Study within each subtype how CSF proteomic markers change over time.
2. Identify blood markers to diagnose AD subtypes, because blood is easier to obtain than CSF, which requires a lumbar puncture.
– Tijms, B. M., Bertens, D., Slot, R. E., Gouw, A. A., Teunissen, C. E., Scheltens, P., et al. Low normal CSF Aβ42 levels predict clinical progression in non-demented subjects. Annals of Neurology 81, 749-753 (2017).
– Willemse, E. A. J., van Maurik, I. S., Tijms, B. M., Bouwman, F. H., Franke, A., Hubeek, I., et al. Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer’s disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring 10, 5563-572 (2018).
– Tijms, B. M., Willemse, E. A. J., Zwan, M. D., Mulder, S. D., Visser, P. J., van Berckel, B. N. M., et al. Unbiased Approach to Counteract Upward Drift in Cerebrospinal Fluid Amyloid-β 1–42 Analysis Results. Clinical Chemistry, 64, 576–585 (2018).
– Jutten, R. J. .. Tijms, BM. Finding Treatment Effects in Alzheimer Trials in the Face of Disease Progression Heterogeneity. Neurology 96, e2673–e2684 (2021).