Our work has focused on finding novel AD biomarkers (1) or biomarker combinations associated with brain amyloidosis, structural brain measures, performance on cognitive tests (2), clinical dementia status and symptom onset (3). Staging AD with a combination of biomarkers has been a major interest because it may allow accurate prediction of AD symptom onset. The lab has been particularly interested in blood-based biomarkers, which recently have been undergoing rapid development (4). 

  1. Schindler SE, Li Y, Todd KW, Herries EM, Henson RL, Gray JD, Wang G, Graham DL, Shaw LM, Trojanowski JQ, Hassenstab JJ, Benzinger TLS, Cruchaga C, Jucker M, Levin J, Chhatwal JP, Noble JM, Ringman JM, Graff-Radford NR, Holtzman DM, Ladenson JH, Morris JC, Bateman RJ, Xiong C, Fagan AM; Dominantly Inherited Alzheimer Network. Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2019 May;15(5):655-665. PMID: 30846386.
  2. Schindler SE, Jasielec MS, Weng H, Hassenstab JJ, Grober E, McCue LM, Morris JC, Holtzman DM, Xiong C, Fagan AM. Neuropsychological measures that detect early impairment and decline in preclinical Alzheimer disease. Neurobiol Aging 56:25-32, 2017. PMID: 28482211.
  3. Schindler SE, Li Y, Buckles VD, Gordon BA, Benzinger TLS, Wang G, Coble D, Klunk WE, Fagan AM, Holtzman DM, Bateman RJ, Morris JC, Xiong C. Predicting symptom onset in sporadic Alzheimer disease with amyloid PET. Neurology. 2021 Nov 2;97(18):e1823-e1834. Epub 2021 Sep 9. PMID: 34504028.
  4. Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C, Fagan AM, Bateman RJ. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019 Oct 22;93(17):e1647-e1659. PMID: 31371569.

Individual characteristics may modify the expression of AD symptoms associated with a particular biomarker level (1-2). Collaborations on this topic have helped our lab to appreciate that models predicting risk for symptomatic AD must account for numerous individual characteristics. Family history, polygenic risk score, comorbidities and race may all modify AD-associated biomarkers and outcomes. 

  1. Schindler SE, Cruchaga C, Joseph A, McCue L, Farias FHG, Wilkins CH, Deming Y, Henson RL, Mikesell RJ, Piccio L, Llibre-Guerra JJ, Moulder KL, Fagan AM, Ances BM, Benzinger TLS, Xiong C, Holtzman DM, Morris JC. African Americans Have Differences in CSF Soluble TREM2 and Associated Genetic Variants. Neurol Genet. 2021 Apr;7(2):e571. PMID: 33884297.
  2. Schindler, S.E., Bateman, R.J. Combining blood-based biomarkers to predict risk for Alzheimer’s disease dementia. Nat Aging 1, 26–28 (2021). https://doi.org/10.1038/s43587-020-00008-0.

The lab is interested in translating AD biomarker research into clinical practice. Schindler participated in a working group to establish appropriate use criteria for CSF biomarkers in the dementia clinic. We evaluated the correspondence of CSF biomarkers as measured by automated Roche Elecsys assays with amyloid PET (1); Elecsys assays are now used in clinical trials and in the dementia clinic. The lab is also interested in the technical aspects of AD biomarker assays that influence accuracy, including assay quality control and lot effects. We found that values for CSF Aβ42 as measured by the widely used INNOTEST assay had increased by ~30% over the past decade (2).

  1. Schindler SE, Gray JD, Gordon BA, Xiong C, Batrla-Utermann R, Quan M, Wahl S, Benzinger TLS, Holtzman DM, Morris JC, Fagan AM. Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging. Alz Dement. Nov;14(11):1460-1469, 2018. PMID: 29501462.
  2. Schindler SE, Sutphen CL, Teunissen C, McCue LM, Morris JC, Holtzman DM, Mulder SD, Scheltens P, Xiong C, Fagan AM. Upward drift in cerebrospinal fluid amyloid beta 42 assay values for more than 10 years. Alz Dement 14(1):62-70, 2018. PMID: 28710906.

See Schindler’s bibliography for a comprehensive list of publications.