title: Dementia mimicking Alzheimer's disease Owing to a tau mutation: CSF and PET findings.
abstract: The objective of the study was to illustrate the utility of positron emission tomography (PET) imaging using [C]PIB and [F]FDDNP together with cerebrospinal fluid (CSF) measures of amyloid-beta1 to 42 (Abeta42), total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) in the in vivo diagnosis of specific dementia syndromes. Two siblings fulfilling diagnostic criteria for familial Alzheimer's disease (AD) were investigated using [C]PIB and [F]FDDNP PET in combination with CSF measures of Abeta42, t-tau and p-tau. PET data were compared with paired [C]PIB and [F]FDDNP data from age-matched sporadic AD patients (n=9) and healthy controls (n=6). [C]PIB retention and CSF levels of Abeta42 in both patients resembled those of controls suggesting the presence of nonamyloid pathology. Genetic testing confirmed the absence of mutations in the presenilin 1 gene in 1 patient; subsequent testing revealed the R406W tau mutation in both individuals leading to a diagnosis of frontotemporal dementia [F]FDDNP retention broadly correlated with CSF levels of t-tau and p-tau. Despite both individuals harbouring the same mutation, [F]FDDNP retention and CSF t-tau and p-tau were elevated in 1 patient, but not in the other. [C]PIB imaging and CSF measures of Abeta42 are useful in refuting the presence of underlying amyloid pathology. This, in combination with elevated levels of CSF t-tau and p-tau, has potential value in differential diagnosis of frontotemporal dementia from AD.
authors.affiliation: Department of Neurology & Alzheimer Centre, VU University Medical Centre, Amsterdam, the Netherlands. n.tolboom@vumc.nl
authors.forename: Nelleke
authors.initials: N
authors.lastname: Tolboom
authors.forename: Esther L G E
authors.initials: EL
authors.lastname: Koedam
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000000981:diagnostic imaging; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography / Q000379:methods; D053764:Presenilin-1 / Q000235:genetics; D013844:Thiazoles; D013912:Threonine / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000378:metabolism
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; C054369:MAPT protein, human; D009570:Nitriles; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D013912:Threonine