Concordance between cerebrospinal fluid biomarkers and [11C]PIB PET in a memory clinic cohort.
BACKGROUND
Two approaches are available for measuring Alzheimer's disease (AD) pathology in vivo. Biomarkers in cerebrospinal fluid (CSF) include amyloid-β1-42 (Aβ42) and tau. Furthermore, amyloid deposition can be visualized using positron emission tomography (PET) and [11C]Pittsburgh compound-B ([11C]PIB).


OBJECTIVE
We investigated concordance between CSF biomarkers and [11C]PIB PET as markers for AD pathology in a memory clinic cohort.


METHODS
We included 64 AD patients, 34 non-AD dementia patients, 22 patients with mild cognitive impairment (MCI), and 16 controls. [11C]PIB scans were visually rated as positive or negative. CSF biomarkers were considered abnormal based on Aβ42 alone (<550 ng/L), a more lenient Aβ42 cut-off (<640 ng/L) or a combination of both Aβ42 and tau ((373 + 0.82 tau)/Aβ42 > 1). Concordance between CSF biomarkers and [11C]PIB PET was determined.


RESULTS
Overall, concordance between [11C]PIB PET and CSF Aβ42 (<550 ng/L) was 84%. In discordant cases, [11C]PIB PET was more often AD-positive than Aβ42. When a more lenient Aβ42 cut-point (<640 ng/L) or a combination of Aβ42 and tau was used, concordance with [11C]PIB PET appeared to be even higher (90% and 89%). This difference is explained by a subgroup of mostly MCI and AD patients with Aβ42 levels just above cut-off. Now, in discordant cases, CSF was more often AD-positive than [11C]PIB PET.


CONCLUSIONS
Concordance between CSF Aβ42 and [11C]PIB PET was good in all diagnostic groups. Discordance was mostly seen in MCI and AD patients close to the cut-point. These results provide convergent validity for the use of both types of biomarkers as measures of AD pathology.
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands.
Marissa
M
Zwan
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands.
Argonde
A
van Harten
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands.
Rik
R
Ossenkoppele
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands.
Femke
F
Bouwman
Department of Epidemiology and Biostatistics, VU University Medical Center, MB Amsterdam, The Netherlands.
Charlotte
C
Teunissen
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands.
Sofie
S
Adriaanse
Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands.
Adriaan
A
Lammertsma
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands.
Philip
P
Scheltens
Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands.
Bart
B
van Berckel
Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands Department of Epidemiology and Biostatistics, VU University Medical Center, MB Amsterdam, The Netherlands.
Wiesje
W
van der Flier
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; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000209:etiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles; D016875:tau Proteins / Q000134:cerebrospinal fluid*
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer's disease; amyloid; cerebrospinal fluid; positron-emission tomography; tau