title: Myelin oligodendrocyte basic protein and prognosis in behavioral-variant frontotemporal dementia.
abstract: OBJECTIVE
  To determine the prognostic utility of tauopathy-associated single nucleotide polymorphisms (SNPs) in sporadic behavioral-variant frontotemporal dementia (bvFTD).
  
  
  METHODS
  Eighty-one patients with sporadic bvFTD were genotyped for tauopathy-associated SNPs at rs8070723 (microtubule-associated protein tau [MAPT]) and rs1768208 (myelin-associated oligodendrocyte basic protein [MOBP]). We performed a retrospective case-control study comparing age at onset and disease duration between carriers of ≥1 polymorphism allele and noncarriers for these SNPs. Subanalyses were performed for autopsied subgroups with tauopathy (n = 20) and TDP-43 proteinopathy (n = 12). To identify a potential biological basis for disease duration, neuroimaging measures of white matter integrity were evaluated (n = 37).
  
  
  RESULTS
  Carriers of risk allele (T) in rs1768208 (i.e., MOBP RA+) had a shorter median disease duration (TC/TT = 5.5 years, CC = 9.5 years; p = 0.02). This was also found in the subset of cases with autopsy-confirmed tauopathies (p = 0.04) but not with TDP-43 proteinopathies (p > 0.1). By comparison, polymorphisms at rs8070723 (MAPT) had no effect on disease duration (p > 0.1), although carriers of protective allele (G) in rs8070723 had a younger median age at onset (AG/GG = 54.5 years, AA = 58 years; p < 0.01). MOBP RA+ patients had increased radial diffusivity in the superior corona radiata and midbrain, and reduced fractional anisotropy in the superior corona radiata as well as superior and inferior longitudinal fasciculi compared with noncarriers (p < 0.01).
  
  
  CONCLUSIONS
  The rs1768208 risk polymorphism in MOBP may have prognostic value in bvFTD. MOBP RA+ patients have more severe white matter degeneration in bvFTD that may contribute to shorter disease duration. Future studies are needed to help confirm these findings.
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia. dirwin@mail.med.upenn.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: EunRan
authors.initials: E
authors.lastname: Suh
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: John
authors.initials: J
authors.lastname: Powers
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Katya
authors.initials: K
authors.lastname: Rascovsky
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Wood
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: From the Penn Frontotemporal Degeneration Center, Department of Neurology (D.J.I., C.T.M., J.P., K.R., E.M.W., M.G.); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Alzheimer's Disease Core Center (D.J.I., C.T.M., E.S., E.M.W., J.B.T., S.E.A., V.M.-Y.L., V.M.V.D., J.Q.T., M.G.); Penn Memory Center, Department of Neurology (S.E.A.); and Brain-Behavior Laboratory, Departments of Psychiatry, Perelman School of Medicine (S.E.A.), University of Pennsylvania, Philadelphia.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C560487:MOBP protein, human; D009185:Myelin Proteins