Suzanne Schindler, MD, PhD
Instructor in Neurology
Alzheimer disease (AD) is the most common cause of dementia in older adults. AD-related brain pathology, which includes the accumulation and deposition of amyloid-b peptide and tau protein, is estimated to begin ~10-20 years before the onset of dementia. Multiple failed drug trials for AD demonstrate that treatment late in the disease course, when patients have significant neuronal damage and dementia, is unlikely to be helpful. However, there is hope that treatment of AD early in the disease course, even before patients have developed symptoms of dementia, will be more effective. So-called “secondary prevention trials for AD” require that we identify individuals with pre-clinical AD (cognitively normal individuals with AD-related brain pathology) using fluid biomarkers or imaging tests. Leading fluid biomarkers for AD include low concentrations of amyloid-b 42 (Ab42) and high concentrations of tau and phosphotau181 (ptau) in the cerebrospinal fluid (CSF). There is also increasing interest in markers of synaptic dysfunction/injury, such as synaptosomal-associated protein-25 (SNAP-25) and neurogranin (NGRN).
One problem with using fluid biomarkers to identify individuals with pre-clinical AD is significant person-to-person variation in absolute analyte levels. We propose to measure CSF biomarkers in individuals who have undergone serial CSF collections and quantify the within-person rate of biomarker change, which will correct for some of the individual variation and may provide a superior predictor of AD-related brain pathology. We have successfully used this approach to observe longitudinal changes in CSF biomarkers during middle-age. We recently obtained funding (R03AG050921, PI Schindler) to measure a battery of biomarkers (Ab40, Ab42, tau, ptau, SNAP-25 and NGRN) in CSF from individuals who were cognitively normal at their baseline CSF collection and have undergone two or more CSF collections as part of their participation in studies of aging and dementia at the Knight Alzheimer’s Disease Research Center (ADRC) at Washington University. Our cohort will include groups of individuals representing the entire adult lifespan, from young (age 29-44), middle-aged (age 45-74) and older (age 75+) individuals so that we can determine the rate of CSF biomarker change for individuals representing the entire adult lifespan.
We aim to define CSF biomarkers change over the entire adult lifespan, including when Ab42 levels begin to decline (consistent with early amyloid deposition), when SNAP-25 and NGRN levels begin to increase (reflecting synaptic injury) and when tau and ptau levels begin to increase (reflecting tangle formation and/or neuronal injury). Linear mixed effects models will be used to test our hypothesis that the rate of change in biomarker levels, rather than single baseline measures, better predict hippocampal volume and cortical thickness by brain MRI, performance on cognitive tests, and progression to AD dementia. Support for this hypothesis would impact efforts to identify individuals with pre-clinical AD for clinical trials and may affect approaches to clinical diagnostic testing for AD dementia.
2015 Washington University Institute of Clinical and Translational Sciences (ICTS) KL2 Career Development Awards Program. Institutional K award funding for two years of research and training.
2014 Interdisciplinary Women’s Health Research Scholar K12 Research fellowship. Institutional K award funding for two years of research and training.
2012 AANF/Robert Katzman Clinical Research Training Fellowship in Alzheimer’s disease. Given by the American Academy of Neurology and Alzheimer’s Association to one junior neurologist every two years to fund further research and training in the area of Alzheimer’s disease.
2012 Irwin Levy Prize for Teaching, Washington University Department of Neurology. Given to a resident who “has consistently established the ability to go above and beyond the call of duty to mentor students and directly impact their attitude and success in this profession.”
2010 Resident of the Year Award, Washington University School of Medicine. Given by the Class of 2011 to ten total residents in recognition of excellence in teaching medical students.
2006 Richard and Mildred Poletsky Education Award, Washington University School of Medicine. Given in honor of a student or fellow working towards a research, clinical and/or other service career focusing on dementing illness.
2005 Barbara Jaschik Award, Washington University School of Medicine. Given in recognition of an outstanding female graduate student in her final year of doctoral research whose thesis has focused on the general area of metabolic regulation.
2003 Class of 2001 award, Washington University School of Medicine. Given in recognition of outstanding accomplishment in the areas of community service and student group activities in the first two years of medical school.
- Fellowship in Dementia: Washington University School of Medicine, St. Louis, Missouri (2012-2014)
- Adult Neurology Residency: Washington University School of Medicine, St. Louis, Missouri (2008-2012)
- Medical Scientist Training (M.D./Ph.D. combined degree program): Washington University School of Medicine, St. Louis, Missouri (2000-2008)
Schindler SE, Holtzman DM. sTREM2: Marking the Tipping Point Between Preclinical AD and Dementia? EMBO Mol Med 8(5): 437-8, 2016.
How J, Blattner M, Fowler S, Wang-Gillam A, Schindler SE. Chemotherapy-associated Posterior Reversible Encephalopathy Syndrome: A case report and review of the literature. Neurologist. 21(6): 112-7, 2016.
Schindler SE, Fagan AM. Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD. Front Neurol 6:142, 2015.
Schindler SE, McCall JG, Yan P, Hyrc KL, Li M, Tucker CL, Lee J-M, Bruchas MR, Diamond MI. Photo-activatable Cre recombinase regulates gene expression in vivo. Sci Reports, 5:13627, 2015.
Schindler SE, McConathy J, Ances BM, Diamond MI. Advances in diagnostic testing for Alzheimer disease. MO Med 110(5):401-5, 2013.
Musiek ES, Schindler SE. Alzheimer disease: current concepts and future directions. MO Med 110(5):395-400, 2013.
Wahrle SE, Jiang H, Parsadanian M, Kim J, Li A, Knoten A, Jain S, Hirsch-Reinshagen V, Wellington CL, Bales KR, Paul SM, Holtzman DM. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest 118(2):671-682, 2008.
Wahrle SE, Shah AR, Fagan AM, Smemo S, Kauwe JSK, Grupe A, Hinrichs A, Mayo K, Jiang H, Thal LJ, Goate AM, Holtzman DM. Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms. Mol Neurodegen 2:7, 2007.
Wahrle SE, Jiang H, Parsadanian M, Hartman RE, Bales KR, Paul SM, Holtzman DM. Deletion of Abca1 increases Ab deposition in the PDAPP transgenic mouse model of Alzheimer’s disease. J Biol Chem 280(52):43236-42, 2005.
Wahrle SE, Jiang H, Parsadanian M, Legleiter J, Han X, Fryer JD, Kowalewski T, Holtzman DM. ABCA1 is required for normal central nervous system apoE levels and for lipidation of astrocyte-secreted apoE. J Biol Chem 279(39):40987-93, 2004.
Wahrle S, Das P, Nyborg AC, McLendon C, Shoji M, Kawarabayashi T, Younkin LH, Younkin SG, Golde TE. Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane domains. Neurobiol Dis 9(1):11-23, 2002.
Dr. Schindler is a neurologist with special interest and training in neurodegenerative disorders including Alzheimer’s disease.