Project Details
Description
PROJECT SUMMARY/ABSTRACT
Great advances are underway in the field of dementia. Symptomatic Alzheimer’s’ disease (AD) can be
diagnosed with a simple blood test. The number of new dementia patients per capita is shrinking in parallel to
public health campaigns to improve brain health. New drugs are emerging that promise to effectively prevent or
treat dementing illness. While these breakthroughs in dementia diagnostics, prevention and treatment are
cause for celebration, hardly anything is known about whether these advances will translate to Native
American (NA) communities, where very little is known about dementia from a biomedical perspective. For
instance, only two NA at the time of this writing have available blood test data in the AD Neuroimaging
Initiative, the largest AD biobank in the United States. Approximately 200 NA have been included in the largest
AD consortium in the country out of over 40,000 participants. This lack of knowledge regarding dementia in NA
is problematic and portends a widening of already severe health disparities. The current study’s central
hypothesis is that American Indians have unique dementia risk factors and a differential effect of APOE ε4 –
the most significant genetic risk factor for AD. These factors will change the epidemiology of dementia and
preclude a “one size fits all” AD blood test using APOE ε4, The first goal of the current project is to determine
what types of dementia exist among NA Tribal Nations, which is currently unknown but is a first-step to
designing and implementing effective brain health policy. The second goal involves measuring the ancestry-
dependent effect of APOE on AD risk and AD biology in NA. AD blood tests utilize the APOE gene along with
direct quantification of the toxic proteins associated with AD to determine a positive or negative result. If
inherited from a European ancestor, having an APOE ε4 allele increases the chances of AD and also
increases the probability of a positive AD blood test result. But if a patient inherits their APOE ε4 gene from an
African ancestor, there is an attenuated impact on accumulation of toxic proteins that define AD. The same
neutral relationship between APOE ε4 and AD likely applies to NA – preliminary data from our group and
others suggest that inheriting an APOE ε4 gene from a NA ancestor similarly does not increase the risk of AD.
If an NA individual undergoes an AD blood test and carries an APOE ε4 allele, will they receive a life-changing
but false diagnosis for a devastating condition? Our study thus will measure the relationship between APOE
and AD risk/biology in NA. As APOE is also a centerpiece of personalized medicine, risk/benefit discussions
for anti-amyloid therapy, trial eligibility, and the target of genetically guided therapies, this study will provide
critical knowledge about the applicability of APOE based medical advances to NA. This is the first study to our
knowledge that attempts to bring American Indian dementia care into the 21st century and provide a
foundation for this understudied group to benefit from the latest advances in diagnosis, prevention treatment of
dementia.
Status | Finished |
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Effective start/end date | 8/15/22 → 4/30/24 |
Funding
- National Institute on Aging: $737,599.00
- National Institute on Aging: $737,599.00
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