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2019 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Stratification of AD and FTLD using the ATN system and Cognitive Markers

Can a novel method for diagnosing Alzheimer’s disease be improved to better distinguish specific disease subtypes?

Katheryn Cousins, Ph.D.
University of Pennsylvania
Philadelphia, PA - United States


The National Institute on Aging and the Alzheimer’s Association (NIA-AA) Research Framework proposal gives an expanded definition of Alzheimer’s disease that incorporates the entire Alzheimer’s disease continuum- from the earliest changes in the brain to late-stage clinical symptoms. The framework proposes shifting the definition of Alzheimer’s disease in living individuals—for use in a research—from one based on cognitive changes and behavioral symptoms to one based on changes in the brain and body. This proposal is about acknowledging that there are biological brain changes that happen 20 years before memory loss is first detected and it stresses that there may be an opportunity to try and treat those biological changes early.
The NIA-AA research framework suggests that biomarkers associated with Alzheimer’s are within the AT(N) system. In this system a) “A” refers to the protein beta-amyloid whose levels accumulates as a hallmark brain change in Alzheimer’s and are measured by either brain scans or in a biological fluid called CSF (cerebrospinal fluid) that surrounds the brain and spinal cord b) “T” refers to protein tau—whose accumulation is another hallmark of Alzheimer’s disease and related dementias— whose levels are measured in CSF or via brain scans c) “N” refers to neurodegeneration (brain damage) which is measured by changes in the brain such as differences in brain volume/thickness, or by measuring the levels of tau in CSF. The ATN biomarker system is based on relationships between biomarkers of amyloid, tau and cell death.
Past studies indicate that individuals with other brain diseases such as frontotemporal dementia (a type of dementia that results in brain cell damage leading to changes in behavior, personality, etc.) may have similar biomarker profiles resembling those with Alzheimer’s. Dr. Katheryn Cousins and her team will develop tests to identify the underlying cause of FTD and Alzheimer’s using several methods including biomarkers, brain scans, demographic factors etc.

Research Plan

Dr. Cousins and colleagues will study how to improve the sensitivity of the CSF biomarker to understand the underlying biological cause of Alzheimer’s and FTD. To do so, first, the researchers will assess how well the NIA-AA research framework currently distinguishes non-amnestic Alzheimer’s (that impacts thinking skills, cognition etc. and not memory) from amnestic Alzheimer’s (that involves memory loss). Dr. Cousins believes that this could be a way to evaluate accuracy of the biomarker results since individuals with non-amnestic Alzheimer’s tend to be younger at disease onset and their genetic as well as demographic makeup resemble individuals with FTD.
The researchers will also evaluate whether adding other methods to detect cognitive impairment such as brain scans, health history etc. — might supplement the results of CSF biomarkers to help better understand the brain changes observed in early-onset compared to late-onset dementia.


The study results could refine our understanding of how dementia may develop in individuals including the age of onset and the symptoms a person experiences. It may also lead to more closely-targeted methods of diagnosing and potentially treating specific dementia types.

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