Posted February 7, 2024

Jagan Pillai, M.D., Ph.D., Cleveland Clinic Foundation

Dr. Jagan Pillai
Dr. Jagan Pillai
(Photo Provided)

Alzheimer’s disease and related dementias cause problems with cognition, or memory and thinking skills, and their complex nature poses a significant healthcare challenge. One of the biggest hurdles for Alzheimer’s disease is the lack of clear-cut tests doctors could use to reliably diagnose the condition. Unlike conditions with straightforward indicators, like over-the-counter tests for COVID-19, Alzheimer’s disease lacks definitive biomarkers, or ways to measure the disease, in its early stages.1 This makes it difficult for doctors to diagnose the disease accurately and early enough for available treatments to be most effective. People with cardiovascular disease, high blood pressure, and diabetes have an increased risk for developing dementia.3 Researchers are working urgently to identify specific measures for these increased risk factors that could reliably enhance early detection and pave the way for more targeted treatments.

Jagan Pillai, M.D., Ph.D., at the Cleveland Clinic Foundation received an FY21 Peer Reviewed Alzheimer’s Research Program, or PRARP, award to investigate potential biomarkers for cognitive decline in diabetic patients and individuals at the earliest stage of Alzheimer’s disease. Specifically, Dr. Pillai hopes to identify a relationship between cholesterol markers in the blood and cerebrospinal fluid and Alzheimer’s disease. Apolipoprotein A1, or ApoA1, is a key protein involved in cholesterol transport and metabolism in the body. ApoA1 is a component of high-density lipoprotein, often referred to as good cholesterol. Dr. Pillai and his team of researchers are attempting to determine whether ApoA1 in blood plasma and cerebrospinal fluid is related to signs of cognition and if those relationships are facilitated by amyloid deposition, issues with blood vessels, or inflammation biomarkers. Amyloid deposition refers to a hallmark of Alzheimer’s disease in which proteins clump together and form abnormal structures, like plaques, in the brain.

Metabolic syndrome is a cluster of conditions that occur together and increase risk of stroke, heart disease, and Type 2 diabetes.2 The relationship between metabolic syndrome biomarkers and the ApoA1 protein could offer clues about how the body handles cholesterol and how these pathways may be related to memory and thinking skills in people with Alzheimer’s disease. Dr. Pillai demonstrated that there is a relationship between metabolic syndrome biomarkers and the rate of cognitive decline in individuals diagnosed with mild cognitive impairment and later stages of Alzheimer’s disease in a recent paper supported by the PRARP award.3 The research team used data from a large project called the Alzheimer’s Disease Neuroimaging Initiative – a study of individuals aged 55 to 90 experiencing various memory issues – to explore the same ApoA1 protein in the FY21 PRARP-funded research. Results from the study indicate both groups of people with mil d cognitive impairment and dementia diagnoses had higher levels of metabolic syndrome biomarkers in the blood, and these levels were associated with a faster decline in cognitive function.3

The research conducted by Dr. Pillai and his team are clarifying vital information that contributes toward the emergence of blood biomarkers for early detection of Alzheimer’s disease and Alzheimer’s disease-related dementias. The ability to identify Alzheimer’s disease in people with elevated risk factors will allow medical providers to offer the best treatments to slow dementia and preserve the quality of life for millions of individuals.


1Earlier Diagnosis. Alzheimer’s Association.

2Metabolic Syndrome. Johns Hopkins Medicine.


3Pillai AJ, Bena J, Bekris L, et al. 2023. Metabolic syndrome biomarkers relate to rate of cognitive decline in MCI and dementia stages of Alzheimer’s disease. Alzheimer’s Research & Therapy 15, 54. doi: 10.1186/s13195-023-01203-y

Public and Technical Abstracts: Apolipoprotein A1 Modifications Related to Cognitive Decline in Type 2 Diabetes and Preclinical Alzheimer’s Disease

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