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Background  Reduced cerebrospinal fluid ( CSF )  β ‐amyloid42 (A β 42) and increased florbetapir positron emission tomography ( PET ) uptake reflects brain A β  accumulation. These biomarkers are correlated with each other and altered in Alzheimer's disease ( AD ), but no study has directly compared their diagnostic performance.    Methods  We examined healthy controls (CN,  N  = 169) versus AD dementia patients ( N  = 118), and stable ( sMCI ; no dementia, followed up for at least 2 years,  N  = 165) versus progressive MCI ( pMCI ; conversion to AD dementia,  N  = 59). All subjects had florbetapir PET (global and regional; temporal, frontal, parietal, and cingulate) and CSF A β 42 measurements at baseline. We compared area under the curve (AUC), sensitivity, and specificity (testing a priori and optimized cutoffs). Clinical diagnosis was the reference standard.    Results   CSF  A β 42 and (global or regional)  PET  florbetapir did not differ in  AUC  ( CN  vs.  AD ,  CSF  84.4%; global  PET  86.9%; difference [95% confidence interval] −6.7 to 1.5).  CSF  A β 42 and global  PET  florbetapir did not differ in sensitivity, but  PET  had greater specificity than  CSF  in most comparisons. Sixteen  CN  progressed to  MCI  and  AD  (six A β  negative, seven A β  positive, and three  PET  positive but  CSF  negative).    Interpretation  The overall diagnostic accuracies of CSF A β 42 and PET florbetapir were similar, but PET had greater specificity. This was because some CN and  sMCI  subjects appear pathological using CSF but not using PET, suggesting that low CSF A β 42 not always translates to cognitive decline or brain A β  accumulation. Other factors, including costs and side effects, may also be considered when determining the optimal modality for different applications.

Diagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer's disease