Takahisa Kanekiyo, M.D., Ph.D.

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SUMMARY

Takahisa Kanekiyo, M.D., Ph.D., studies the pathogenic pathways of age-related neurodegenerative diseases and neurovascular diseases. Specifically, Dr. Kanekiyo focuses on the contributions of apolipoprotein E (APOE) and APOE receptors in Alzheimer's disease (AD) and cerebral amyloid angiopathy. His research aims to determine how aging, sex and APOE isoforms influence cerebrovascular functions as well as disease development and progression using biochemical and molecular approaches through in vitro systems and disease models, with the ultimate goal of developing effective therapies for these diseases. Dr. Kanekiyo also investigates the disease pathogenesis in postmortem brain samples and models through patient-derived induced pluripotent stem cells (iPSCs).

Focus areas

• APOE and cerebrovascular functions in Alzheimer's disease. Impairments of the cerebrovascular system likely contribute to AD pathogenesis. APOE4 is the strongest genetic risk factor for AD, where APOE4 not only exacerbates amyloid-β (Aβ) accumulation in the brain but also disturbs cerebrovascular function. Dr. Kanekiyo studies the roles of APOE isoforms and cerebrovascular functions in the disease pathogenesis.
• APOE and LRP1 in Alzheimer's disease. ApoE receptors regulate AD pathogenesis by Aβ-dependent and independent mechanisms. In particular, the low-density lipoprotein receptor-related protein 1 (LRP1) is a major APOE receptor expressed in diverse brain cell types. Dr. Kanekiyo's research aims to determine the roles of the APOE-LRP1 axis in AD pathogenesis.
• ABCA7 and Alzheimer's disease. Recent genome-wide association studies identified that the ATP-binding cassette transporter A7 (ABCA7) gene as well as APOE are strongly associated with the risk of late-onset AD. Thus, Dr. Kanekiyo also studies how ABCA7 loss of function impacts AD pathogenesis.

Significance to patient care

In our aging society an increasing number of patients have neurodegenerative and neurovascular diseases. Dr. Kanekiyo's hope is that his research contributes to a better understanding of the molecular mechanisms in the disease pathogenesis, and provides novel targets to develop effective therapeutic interventions for these diseases.

Professional highlights

• Standard award, RNA Discovery and Translation Program, Mayo Clinic in Florida, 2024-2027.
• Scientist development grant, American Heart Association, 2015-2018.
• New investigator research grant, Alzheimer's Association, 2014-2016.
• Young investigator award, Alex's Lemonade Stand Foundation, 2013-2015.
• Postdoctoral fellowship:
  • American Heart Association, 2009-2011.
  • American Health Assistance Foundation, 2009.