title: Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy.
abstract: BACKGROUND
  Elevated CSF τ is considered a biomarker of neuronal injury in newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI) criteria. However, previous studies have failed to detect alterations of τ species in other primary tauopathies. We assessed CSF τ protein abnormalities in AD, a tauopathy with prominent Aβ pathology, and progressive supranuclear palsy (PSP), a primary tauopathy characterised by deposition of four microtubule-binding repeat (4R) τ with minimal Aβ pathology.
  
  
  METHODS
  26 normal control (NC), 37 AD, and 24 patients with PSP participated in the study. AD and PSP were matched for severity using the clinical dementia rating sum of boxes (CDR-sb) scores. The INNO BIA AlzBio3 multiplex immunoassay was used to measure CSF Aβ, total τ, and ptau181. Additional, novel ELISAs targeting different N-terminal and central τ epitopes were developed to examine CSF τ components and to investigate interactions between diagnostic group, demographics and genetic variables.
  
  
  RESULTS
  PSP had lower CSF N-terminal and C-terminal τ concentrations than NC and AD measured with the novel τ ELISAs and the standard AlzBio3 τ and ptau assays. AD had higher total τ and ptau levels than NC and PSP. There was a gender by diagnosis interaction in AD and PSP for most τ species, with lower concentrations for male compared to female patients.
  
  
  CONCLUSIONS
  CSF τ fragment concentrations are different in PSP compared with AD despite the presence of severe τ pathology and neuronal injury in both disorders. CSF τ concentration likely reflects multiple factors in addition to the degree of neuronal injury.
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Wagshal
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: Sethu
authors.initials: S
authors.lastname: Sankaranarayanan
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Guss
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: Tracey
authors.initials: T
authors.lastname: Hall
authors.affiliation: Kyowa Hakko Kirin Pharma, Inc., Princeton, New Jersey, USA.
authors.forename: Flora
authors.initials: F
authors.lastname: Berisha
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Iryna
authors.initials: I
authors.lastname: Lobach
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Karydas
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Voltarelli
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Scherling
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Heuer
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA Tanz Center for Research in Neurodegenerative disease, University of Toronto, Toronto, Canada.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Tartaglia
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Miller
authors.affiliation: Department of Psychiatry, Semel Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ahlijanian
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: Jere
authors.initials: J
authors.lastname: Meredith
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000235:genetics; D010766:Phosphorylation; D011379:Prognosis; D012016:Reference Values; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid* / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D024801:Tauopathies / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's Disease; CSF