Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding.
The purpose of this study was to investigate the potential relationships between cerebrospinal fluid (CSF) measurements of beta-amyloid-1-42 (Abeta(1-42)) and total tau to (11)C-Pittsburgh compound B ((11)C-PiB) and 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ((18)F-FDDNP) binding as measured using PET.


METHODS
A total of 37 subjects were included, consisting of 15 patients with Alzheimer disease (AD), 12 patients with mild cognitive impairment, and 10 healthy controls. All subjects underwent a lumbar puncture and PET using both (11)C-PiB and (18)F-FDDNP. For both PET tracers, parametric images of binding potential were generated. Potential associations of CSF levels of Abeta(1-42) and tau with (11)C-PiB and (18)F-FDDNP binding were assessed using Pearson correlation coefficients and linear regression analyses.


RESULTS
For both global (11)C-PiB and (18)F-FDDNP binding, significant correlations with CSF levels of Abeta(1-42) (r = -0.72 and -0.37, respectively) and tau (r = 0.58 and 0.56, respectively) were found across groups (all P < 0.001, except P < 0.05 for correlation between (18)F-FDDNP and Abeta(1-42)). Linear regression analyses showed that, adjusted for regional volume, age, sex, and diagnosis, global (11)C-PiB uptake had an inverse association with Abeta(1-42) CSF levels (standardized beta = -0.50, P < 0.001), whereas there was a positive association between global (18)F-FDDNP binding and tau CSF levels (standardized beta = 0.62, P < 0.01).


CONCLUSIONS
The good agreement between these 2 different types of biomarkers (i.e., CSF and PET) provides converging evidence for their validity. The inverse association between (11)C-PiB and CSF tau Abeta(1-42) confirms that (11)C-PiB measures amyloid load in the brain. The positive association between (18)F-FDDNP and CSF tau suggests that at least part of the specific signal of (18)F-FDDNP in AD patients is due to tangle formation.
Tolboom
Nelleke
N
Departments of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands. ntolboom@vumc.nl
van der Flier
Wiesje M
WM
Yaqub
Maqsood
M
Boellaard
Ronald
R
Verwey
Nicolaas A
NA
Blankenstein
Marinus A
MA
Windhorst
Albert D
AD
Scheltens
Philip
P
Lammertsma
Adriaan A
AA
van Berckel
Bart N M
BN
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D008297:Male; D009570:Nitriles / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013223:Statistics as Topic; D013844:Thiazoles; D014018:Tissue Distribution; D016875:tau Proteins / Q000134:cerebrospinal fluid*
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; D009570:Nitriles; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins