Objective To investigate the diagnostic accuracy and correlation between cerebrospinal fluid biomarkers and ¹¹C-Pittsburgh compound-B (PIB) PET/CT imaging in Alzheimer disease (AD). The optimal cut-off values of cerebrospinal fluid biomarkers are also determined.

Methods The clinical data of 66 subjects who underwent ¹¹C-PIB PET/CT imaging and lumbar puncture at the General Hospital of Northern Theater Command from January 2011 to March 2020 were retrospectively analyzed. The participants included 32 males and 34 females aged 61–82 (71.0±3.4) years and were divided into the AD patient group (n=50) and the healthy control group (n=16) according to established criteria. Enzyme-linked immunosorbent assay was used to detect levels of the cerebrospinal fluid biomarkers α-synuclein (α-syn), β-amyloid (Aβ) 40, Aβ42, t-tau and p-tau. The level ratios of t-tau to Aβ42 (t-tau/Aβ42) and Aβ42 to Aβ40 (Aβ42/Aβ40) were calculated. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic optimal cut-off value, sensitivity, and specificity of the cerebrospinal fluid biomarkers. ¹¹C-PIB PET/CT images were analyzed. The average Aβ deposition standardized uptake value ratio (SUVR) was calculated, and the accuracy and correlation between the two groups of cerebrospinal fluid biomarkers and ¹¹C-PIB PET/CT imaging in the diagnosis of AD were analyzed. The levels of cerebrospinal fluid biomarkers between the two groups was compared by independent-sample t test, and the count data were compared by χ² test. Pearson correlation coefficients were calculated for correlation analysis, and consistency was determined using the Kappa test.

Results The levels of cerebrospinal fluid biomarkers α-syn, t-tau andp-tau as well as t-tau/Aβ42 in the AD patient group were higher than those in the healthy control group (t=2.315, 4.001, 2.336, 3.291, all P<0.01), while the Aβ42 level and Aβ42/Aβ40 were lower than those in the healthy control group (t=−5.443, −3.487, both P<0.05). T-tau/Aβ42 revealed the highest diagnostic accuracy for AD (AUC=0.892, P<0.001), followed by Aβ42/Aβ40 and α-syn (AUC=0.865, 0.795, both P<0.01). The optimal cut-off values of t-tau/Aβ42 and Aβ42/Aβ40 were 0.509 and 0.072, respectively, and the aptimal cut-off value of α-syn was 465 pg/mL. The sensitivities of t-tau/Aβ42, Aβ42/Aβ40, α-syn and ¹¹C-PIB PET/CT imaging for predicting AD were 80.0% (40/50), 76.0% (38/50), 74.0% (37/50) and 78.0% (39/50), respectively. The sensitivities of the first three methods in combination with ¹¹C-PIB PET/CT imaging for predicting AD were 96.0% (48/50), 94.0% (47/50) and 94.0% (47/50), respectively, which were all higher than a single method (χ²=5.316–7.440, all P<0.05). The combined diagnostic accuracy of t-tau/Aβ42 and ¹¹C-PIB PET/CT imaging was greater than that of a single diagnostic method (93.9% vs. 80.3%, 93.9% vs. 77.2%), and the difference noted was statistically significant (χ²=5.469, 7.439, both P<0.05). T-tau/Aβ42, Aβ42/Aβ40 and α-syn level were significantly correlated with ¹¹C-PIB PET/CT SUVR (r=0.555, −0.451, 0.445, all P<0.01). The Kappa value of diagnostic consistencies of t-tau/Aβ42, Aβ42/Aβ40 and α-syn with ¹¹C-PIB PET/CT imaging were 0.769, 0.623 and 0.587, respectively (all P<0.001). Among the criteria considered, t-tau/Aβ42 demonstrated great diagnostic consistency with ¹¹C-PIB PET/CT.

Conclusions T-tau/Aβ42, Aβ42/Aβ40 and α-syn are ideal diagnostic criteria for AD. Combining these parameters with ¹¹C-PIB PET/CT imaging could improve the accuracy of AD diagnosis.