A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer’s Disease - 21/11/24
, K. Ishii 2, K. Ito 3, T. Ikeuchi 4, H. Matsuda 5, 20, T. Iwatsubo 6, A. Iwata 6, 21, R. Ihara 6, K. Suzuki 6, 22, K. Kasuga 4, Y. Ikari 1, 7, Y. Niimi 6, H. Arai 8, A. Tamaoka 9, Y. Arahata 3, Y. Itoh 10, H. Tachibana 11, Y. Ichimiya 12, S. Washizuka 13, T. Odawara 14, K. Ishii 15, K. Ono 16, T. Yokota 17, A. Nakanishi 18, E. Matsubara 19, H. Mori 10, H. Shimada 10
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Abstract |
Background |
PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the “ATN” (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer’s disease (AD).
Objective |
Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients.
Measurements |
A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65–84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aβ1–42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF.
Results |
The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET−/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders.
Conclusion |
Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.
Il testo completo di questo articolo è disponibile in PDF.Key words : Alzheimer’s disease, PET, CSF biomarker, amyloid, tau
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| Conflict of interest: The following conflicts of interest are disclosed by the authors. Senda reports provision of devices, cassettes, and precursors from Avid/ Eli Lilly Japan and GE, funding as PI of clinical trials sponsored by Eli Lilly, Eisai, Biogen, Cerveau and Merck, as well as leadership role in the Japanese Society of Nuclear Medicine as board member, congress chair and committee chair. Ikeuchi reports grants from AMED (JP19dk0207020, JP20dk0202028, JP20dm0207073). Matsuda reports a grant from AMED (19dk0207020h0005), intramural grants from National Center of Neurology and Psychiatry, and an entrusted research fund from Nihon Medi-Physics Co. Ltd. Iwatsubo reports a grant from an anonymous Foundation. Iwata reports grants from AMED (19dk0207020h0005, 16dk0207028h0001). Ikari is a full time employee of CMIC Inc. as well as graduate student of Osaka University. Washizuka reports research funding from AMED and pharmaceutical companies including Otsuka, Eisai, Pfizer, Daiichi-Sankyo, Tsumura, Mochida, Astellas, Shionogi, Takeda, Sumitomo-Dainippon, as well as honoraria from such pharmaceutical companies. Kazunari Ishii reports honoraria from Nihon Medi-Physics. Yokota reports licensing and collaboration research with Takeda Pharmaceutical Company. Nakanishi reports research funding from Eisai and Elli Lilly Japan as well as leadership role as a director in the Japan Society for Dementia Research. Shimada reports grants from AMED (19dk0207020h0005, 20dk0207028h0005). The other authors have nothing to disclose. |
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| Funding: This study was financially supported by grants from Japan Agency for Medical Research and Development (AMED) 19dk0207020h0005, 20dk0202028h0005 and 20dm0207073h003, as well as by an anonymous Foundation. |
Vol 8 - N° 4
P. 495-502 - Aprile 2021 Ritorno al numero
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