Investigating African American-specific AD-related ABCA7 Variants Using Isogenic hiPSCs

Overview

About this study

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:

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • African American descent.
  • Minimum of 50 years of age.
  • Have neuropsychological documentation of their cognitive/clinical status.

Exclusion Criteria:

  • Less than 50 years of age.
  • Unwilling to provide consent.
  • Diagnostic uncertainty (which may be due to a complicating medical condition such as metastatic cancer, end stage organ disease, concurrent neuropsychiatric disease (or other medical factor). 

More information

Publications

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CLS-20521066

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