Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease.
OBJECTIVE
To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).


METHODS
From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.


RESULTS
The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03-0.12, p<0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.


CONCLUSIONS
Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.


METHODS
This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden. sebastian.palmqvist@med.lu.se
Sebastian
S
Palmqvist
Henrik
H
Zetterberg
Niklas
N
Mattsson
Per
P
Johansson
Lennart
L
Minthon
.
Kaj
K
Blennow
Mattias
M
Olsson
oskar.hansson@med.lu.se.
Oskar
O
Hansson
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011877:Radionuclide Imaging; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins