Lynn Bekris, PhD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Alzheimer's disease is a devastating progressive neurodegenerative disorder that impacts millions of people worldwide. It is is now regarded as a continuum of pathological changes that are defined by pathological Aβ and Tau accumulation in the brain with a long pre-symptomatic period of 10 to 20 years.
- A decades long continuum of progressive pathological changes offers the unique opportunity to treat the neurodegenerative disease early before cognitive decline.
- The problem is that genetic evidence strongly suggests there can be other heterogeneous pathological features, such as inflammation, but a reliable blood-based biomarker of inflammation in Alzheimer's disease remains elusive.
- A patient may also have a heterogenous mixture of pathologies that include hallmarks of multiple neurodegenerative diseases, including Alzheimer's disease, Dementia with Lewy Bodies, and vascular dementia, but reliable blood-based biomarkers specific to these pathologies remain elusive.
- The Bekris lab research goal is to identify specific biomarker signatures that tease apart the heterogeneous nature of early pre-symptomatic disease for tracking disease progression, therpeutically targeting the disease and monitoring treatment effectiveness.
- Dr. Bekris is the director of the Cleveland Alzheimer's Disease Research Center (CADRC) Biomarker Core and the co-director of the Cleveland Clinic Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease Biobank (LRCBH-biobank). She is also a co-investigator of the Dementia with Lewy Body Consortium (DLBC).
Bekris lab is focused on Alzheimer's Disease Biomarker Discovery and uses clinical and experimental approaches to demonstrate the feasibility of genetic and epigenetic factors underlying soluble protein expression as either potential early stage drug targets or early biomarkers of disease risk, progression and therapeutic outcomes.
- TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42 in HMC3 cells. Mol Immunol. 2021
- TNFRSF1B Gene Variants and Related Soluble TNFR2 Levels Impact Resilience in Alzheimer's Disease.
Front Aging Neurosci. 2021.
- An Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome: A Preliminary Report. Weber GE, Koenig KA, Khrestian M, Shao Y, Tuason ED, Gramm M, Lal D, Leverenz JB, Bekris LM. J Immunol. 2020.
- Key inflammatory pathway activations in the MCI stage of Alzheimer's disease. Pillai JA, Maxwell S, Bena J, Bekris LM, Rao SM, Chance M, Lamb BT, Leverenz JB; Alzheimer’s Disease Neuroimaging Initiative. Ann Clin Transl Neurol. 2019.
- Soluble TREM2 and biomarkers of central and peripheral inflammation in neurodegenerative disease. Bekris LM, Khrestian M, Dyne E, Shao Y, Pillai JA, Rao SM, Bemiller SM, Lamb B, Fernandez HH, Leverenz JB. J Neuroimmunol. 2018.
- DNA methylation of TOMM40-APOE-APOC2 in Alzheimer's disease. Shao Y, Shaw M, Todd K, Khrestian M, D'Aleo G, Barnard PJ, Zahratka J, Pillai J, Yu CE, Keene CD, Leverenz JB, Bekris LM. J Hum Genet. 2018.
- Epigenetic signature and enhancer activity of the human APOE gene. Yu CE, Cudaback E, Foraker J, Thomson Z, Leong L, Lutz F, Gill JA, Saxton A, Kraemer B, Navas P, Keene CD, Montine T, Bekris LM. Hum Mol Genet. 2013
Dr. Bekris’ team found that patterns of sTREM2-related inflammatory activity were specific to Alzheimer’s disease stages.
National Institute on Aging Awards $15.4 Million to Continue Support for Cleveland Alzheimer’s Disease Research Center
The multi-institution collaboration, which includes Dr. Bekris’ team, aims to accelerate research for Alzheimer’s disease and related dementias.
Dr. Bekris’ team has found that Alzheimer’s disease resilience may be modulated by interactions between a TNFRSF1B gene variant and the protein sTNFR2.
Dr. Bekris’s team will study the protein TREM2 as a biomarker of inflammation in pre-symptomatic and early symptomatic stages of Alzheimer’s disease.
With a new $4 million grant, Drs. Cheng, Bekris and Leverenz will develop and utilize artificial intelligence tools to identify novel drug targets and repurposable drugs for Alzheimer’s disease.