ALZHEIMER DISEASE & LIPIDS


In a healthy brain neurons, astrocytes and microglia closely work together by the exchange of molecules and proteins. Neurons are the cells responsible for transmitting information, microglia are the immune cells of the brain and astrocytes  are the homeostatic regulators. 

In late stages of Alzheimer's disease and related dementias, neurons eventually die and cause memory problems. However, the cause for this death remains unknown. Over the last years, it has become increasingly clear that problems in the Alzheimer's brain start with changes in microglia and astrocytes. In addition to the well known Amyloid and Tau pathology, glial lipid accumulation is a major pathology of Alzheimer's. In fact, Alois Alzheimer had already described lipid saccules as a characteristic of the Alzheimer’s Disease in 1907.  Over recent years, our work and the work of our colleagues, has refocused the attention of the field towards lipids as one of the early drivers of Alzheimer's disease. In our lab we aim to 1) understand how changes in lipid metabolism may drive Alzheimer's disease and related dementias and 2) develop lipid-targeting interventions to treat these brain disorders.

IPSC to Drug Discovery Pipeline

We use human iPSC-derived models to study Alzheimer's disease and other neurodegenerative disorders. In a typical workflow we will introduce genetic variants associated with disease into the genome of control iPSC and differentiate these iPSCs to neurons, microglia or astrocytes.  Subsequently we aim to identify a disease-relevant phenotype (often trough unbiased multiomics profiling) and develop a phenotypic read-out that can be used in a cellular drug screening platforms. Lastly, we perform compound screens (repurposed, novel drugs) to identify novel candidate interventions. 

So far we have been successful in screening for Tau modulators in neurons, leading to phase 2a clinical trial with low-dose Efavirenz. Ongoing projects include multiomic profiling of ApoE4 astrocytes & microglia and understanding lipid & AD pathology relationships in more detail. 

Just some nice pictures of our lab

Rik van der Kant

Rik van der Kant undertook his Bachelor's & Master degrees at the Radboud Univeristy in Nijmegen. He then obtained his PhD degree in cell biology at the Netherlands Cancer Institute in Amsterdam under the supervision of Jacques Neefjes. After graduating in 2013, he moved to San Diego for postdoctoral training in the lab of Larry Goldstein (UCSD) to work with iPSC-models of Alzheimer's disease. Rik is currently an assistant professor with a joint position at the Amsterdam UMC Alzheimer Center and the CNCR at the VU university