The immune system is significantly involved in multiple neurodegenerative diseases such as Alzheimer’s. Yet many of the immune “cell-types” are extremely heterogenic and currently remain uncharacterized. A global and unbiased in vivo characterization of immune cell types involved in neuropathology is crucial for understanding disease progression. In recent work, we used single cell RNA sequencing technology for Ab initio characterization of immune cells in various tissues. Here, we propose to uncover the immune cells and regulatory mechanisms involved in neurodegenerative diseases using massively parallel single cell RNA-sequencing. Preliminary results show differential cell states and gene expression between healthy and disease cells from the brain of Alzheimer’s mouse models. Unbiased classification of immune cells will enable better understanding of the course of the disease and will enable to explore novel therapeutic options. Finally if successful this approach will further be applicable to other neurodegenerative diseases such as ALS and schizophrenia.