title: Frontotemporal dementia with the V337MMAPTmutation: Tau-PET and pathology correlations.
abstract: OBJECTIVE
  To assess the efficacy of [18F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT)mutation.
  
  
  METHODS
  MAPTmutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [18F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies. We describe clinical, structural MRI, and [18F]AV1451 PET findings in a V337MMAPTmutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337MMAPTcarrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD andMAPTV337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [18F]AV1451 imaging.
  
  
  RESULTS
  We found a strong association between topography and degree of [18F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of [18F]AV1451 binding in the proband and a strong association between the proband's clinical presentation and the extent of regional brain atrophy and tau accumulation as assessed by structural brain MRI and [18F]AV1451PET.
  
  
  CONCLUSIONS
  Our study supports the usefulness of [18F]AV1451 to characterize tau pathology in at least a subset of pathogenicMAPTmutations.
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL. Salvatore.Spina@ucsf.edu.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spina
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Schonhaut
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Rik
authors.initials: R
authors.lastname: Ossenkoppele
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Neil
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazaris
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: David C
authors.initials: DC
authors.lastname: Perry
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.affiliation: From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002243:Carbolines; D017809:Fatal Outcome; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002243:Carbolines; C054369:MAPT protein, human; D019275:Radiopharmaceuticals; D016875:tau Proteins; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole