Daniel S Marcus

Publications (2)53.3 Total impact

• Article: Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network.

  John C Morris, Paul S Aisen, Randall J Bateman, Tammie L S Benzinger, Nigel J Cairns, Anne M Fagan, Bernardino Ghetti, Alison M Goate, David M Holtzman, William E Klunk, [......], John M Ringman, Martin N Rossor, Stephen Salloway, Peter R Schofield, Natalie J Selsor, Reisa A Sperling, Michael W Weiner, Chengjie Xiong, Krista L Moulder, Virginia D Buckles
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  ABSTRACT: The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort.
  Clinical investigation. 10/2012; 2(10):975-984.
• Article: Clinical and biomarker changes in dominantly inherited Alzheimer's disease.

  Randall J Bateman, Chengjie Xiong, Tammie L S Benzinger, Anne M Fagan, Alison Goate, Nick C Fox, Daniel S Marcus, Nigel J Cairns, Xianyun Xie, Tyler M Blazey, [......], Eric McDade, Ralph N Martins, Colin L Masters, Richard Mayeux, John M Ringman, Martin N Rossor, Peter R Schofield, Reisa A Sperling, Stephen Salloway, John C Morris
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  ABSTRACT: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.).
  New England Journal of Medicine 07/2012; 367(9):795-804. · 53.30 Impact Factor