Genomic Medicine Institute - Center for Personalized Genetic Healthcare

Identifying Genetic Variants in Alzheimer's patients

Dr. Bekris and her team are looking for treatments that prevent weakening cognitive function

Alzheimer disease (AD) progression includes memory loss and cognitive decline that eventually impacts a person’s ability to perform basic daily activities. Without a medical breakthrough to prevent or cure the disease the number of people age 65 and older with Alzheimer disease is predicted to almost triple, from 5.2 million to about 13.8 million by 2050.

Beyond the three major genes known to cause Alzheimer’s, APP, PSEN1, and PSEN2, there is an additional set of genes associated with late-onset Alzheimer’s. APOE is the strongest genetic risk factor to be discovered. However, about 38% of Alzheimer’s patients diagnosed after the age of 65 do not carry APOE suggesting that there are many more genetic variants to be identified. Multiple genetic variants have been identified, but their association with AD risk is much weaker than APOE. Thissuggests that many critical genetic variants are yet to be discovered.

Dr. Bekris’ research at the Genomic Medicine Institute is focused on identifying and evaluating the functional impact of genetic and epigenetic markers in Alzheimer’s. Her research group has identified multiple genetic variants associated with AD related biomarkers as well as small non-protein coding RNAs, called microRNA. MicroRNA is present in plasma and is uniquely found in patients with AD.

Along with the research on biomarkers, Bekris’ Lab has developed libraries for experimental functional testing of genetic variants, including libraries of various APOE geneticvariants. These libraries help tease apart the functional impact of each genetic variant and how they might disrupt normal function or how certain small molecules might correct this disruption of function.

There is no treatment that stops cognitive decline in Alzheimer disease or other dementias at this time. Current AD therapeutics only treat symptoms of the disease. Biomarkers found in blood and cerebrospinal fluids are used to help find treatments that prevent cognitive decline and are essential for:

  • Detecting changes that occur early in the disease process before memory loss and cognitive decline
  • Deciphering the mechanisms underlying these early changes for therapeutic target identification
  • Monitoring therapeutic success

The Center for Brain Health Biobank (CBH-Biobank) was opened in August of 2014 under the direction of Drs. Lynn Bekris of the Genomic Medicine Institute and James Leverenz of the Lou Ruvo Center for Brain Health.  The overall goal of the CBH-Biobank is to “bank” biofluids and other tissues from well-characterized participants for rapid availability for research studies, including biomarker studies. 

The strength of this biobank is the detailed clinical characterization of many of the participants (systematic medical examinations and other testing such as formal cognitive assessment) and the collection of a wide variety of biospecimens (e.g. plasma, serum, DNA, cerebrospinal fluid, white blood cells, lymphoblast cell lines, brain).  While the CBH Biobank focus is on normal aging and neurodegeneration such as, Alzheimer’s and Parkinson’s disease, other disorders such as traumatic brain injury are also collected.  Currently the CBH-Biobank contains over 35,000 biospecimens from 540 individuals.  Investigators interested in learning more about the CBH-Biobank or wish to apply for biospecimens can contact the CBH-Biobank Coordinator Jessica Lee (

Cleveland Clinic Genomic Medicine Institute

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Appointment line: 216.636.1768 or 800.998.4785

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