Richard J. Caselli, M.D.

The purpose of this study is to study the structure and biochemistry of the brain and/or bodily fluid and tissue after death.  Comparison of specimens from normal and diseased individuals provide essential clues that lead to a greater understanding of the diseased state which, in turn, will lead to new ideas for therapy.

This study aims to obtain EEG data on individuals at all stages of AD from preclinical through severe dementia.

In this proposal, we will generate hiPSCs from AA patients and use our TREE-based approaches to introduce AA-associated variants into isogenic hiPSCs. In turn, we will use these isogenic hiPSC lines in a 3-D cortical model to address the following hypothesis-testing questions: (1) Does the presence of specific ABCA7 variants modulate disease-related phenotypes in a hiPSC-based system? (2) Are the risk modifying effects of the ABCA7 variants mediated through cell-autonomous or non-autonomous mechanisms? (3) Do these ABCA7 variants exert their effects through modulation of Aβ processing, secretion, and uptake? (4) What is the effect of these ABCA7 variants as it relates to tau-phosphorylation? (5) Are there transcriptional targets that are independently influenced by the presence of specific ABCA7 variants? To address these questions, we will leverage the collaborative stem cell engineering and neurodegenerative disease modeling expertise of Dr. Brafman as well the clinical neurobiology expertise of Dr. Caselli in the following specific aims:

The purpose of this study is to use a specific gene panel to assist in the diagnosis of a hereditary form of young onset dementia.