Brain Amyloid-β Deposition and Blood Biomarkers in Patients with Clinically Diagnosed Alzheimer’s Disease

Article type: Research Article

Authors: Li, Wei-Wei^a | Shen, Ying-Ying^a | Tian, Ding-Yuan^a | Bu, Xian-Le^a | Zeng, Fan^a | Liu, Yu-Hui^a | Chen, Yang^a | Yao, Xiu-Qing^a | Li, Hui-Yun^a | Chen, Dong-Wan^a | Zhou, Fa-Ying^a | Yang, Heng^a | Li, Qi-Ming^b | Bao, Wei-Qi^e | Guan, Yi-Hui^e | Zhou, Hua-Dong^a | Jin, Rong-Bing^{b; *} | Wang, Yan-Jiang^{a; c; d; *}

Affiliations: [a] Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China | [b] Department of Nuclear Medicine, Daping Hospital, Third Military Medical University, Chongqing, China | [c] State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing, China | [d] Centre for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Science, Shanghai, China | [e] PET Center, Huashan Hospital, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Yan-Jiang Wang, Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China. E-mail: [email protected] and Rong-Bing Jin, Department of Nuclear Medicine, Daping Hospital, Third Military Medical University, Chongqing, China. E-mail: [email protected].

Abstract: Brain amyloid-β (Aβ) deposition is a hallmark to define Alzheimer’s disease (AD). We investigated the positive rate of brain amyloid deposition assessed with 11C-Pittsburgh compound (PiB)-PET and blood Aβ levels in a cohort of probable AD patients who were diagnosed according to the 1984 NINCDS-ADRDA criteria. Eighty-four subjects with a clinical diagnosis of probable AD dementia, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) status were subjected to PiB-PET and 18F-fluorodeoxyglucose (FDG)-PET scans. Plasma biomarkers of Aβ42, Aβ40, and T-tau were measured using single molecule array technology. The positive rate of PiB-PET, the associations between PiB-PET status and FDG-PET, plasma biomarkers, and clinical manifestations were analyzed. PiB-PET was positive in 77.36% of probable AD patients, 31.80% of MCI patients, and 0 of NC. Plasma Aβ42/Aβ40 ratio was associated with PiB-PET, the ROC curve analysis revealing an AUC of 0.77 (95% CI: 0.66–0.87), with a sensitivity of 82% and specificity of 64%. Some clinical manifestations were associated with PiB-PET imaging. Our findings indicate that only three-fourths of patients diagnosed with probable AD fit the pathological criteria, suggesting that we should be cautious regarding the accuracy of AD diagnosis when no biomarker evidence is available in our clinical practice.

Keywords: Alzheimer’s disease, amyloid-beta, amyloid PET, blood biomarkers, diagnosis, mild cognitive impairment, probable AD dementia, tau

DOI: 10.3233/JAD-190056

Journal: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 169-178, 2019