title: Can MRI screen for CSF biomarkers in neurodegenerative disease?
abstract: OBJECTIVE
  Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) may have overlapping clinical presentations despite distinct underlying neuropathologies, thus making in vivo diagnosis challenging. In this study, we evaluate the utility of MRI as a noninvasive screening procedure for the differential diagnosis of AD and FTLD.
  
  
  METHODS
  We recruited 185 patients with a clinically diagnosed neurodegenerative disease consistent with AD or FTLD who had a lumbar puncture and a volumetric MRI. A subset of 32 patients had genetic or autopsy-confirmed AD or FTLD. We used singular value decomposition to decompose MRI volumes and linear regression and cross-validation to predict CSF total tau (tt) and β-amyloid (Aβ(1-42)) ratio (tt/Aβ) in patients with AD and patients with FTLD. We then evaluated accuracy of MRI-based predicted tt/Aβ using 4 converging sources including neuroanatomic visualization and categorization of a subset of patients with genetic or autopsy-confirmed AD or FTLD.
  
  
  RESULTS
  Regression analyses showed that MRI-predicted tt/Aβ is highly related to actual CSF tt/Aβ. In each group, both predicted and actual CSF tt/Aβ have extensively overlapping neuroanatomic correlates: low tt/Aβ consistent with FTLD is related to ventromedial prefrontal regions while high tt/Aβ consistent with AD is related to posterior cortical regions. MRI-predicted tt/Aβ is 75% accurate at identifying underlying diagnosis in patients with known pathology and in clinically diagnosed patients with known CSF tt/Aβ levels.
  
  
  CONCLUSIONS
  MRI may serve as a noninvasive procedure that can screen for AD and FTLD pathology as a surrogate for CSF biomarkers.
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, USA. mcmillac@mail.med.upenn.edu
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.forename: Brian
authors.initials: B
authors.lastname: Avants
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanoswki
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid / Q000473:pathology / Q000523:psychology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000523:psychology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins