Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort
Abstract Background Plasma biomarkers offer a promising alternative to amyloid beta (Aβ) positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers for diagnosing Alzheimer’s disease (AD). This cross-sectional study assessed the utility of multiple plasma biomarkers for diagnosing an...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-025-01778-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850137818433585152 |
|---|---|
| author | Masahito Kubota Shogyoku Bun Keisuke Takahata Shin Kurose Yuki Momota Yu Iwabuchi Toshiki Tezuka Hajime Tabuchi Morinobu Seki Yasuharu Yamamoto Ryo Shikimoto Yu Mimura Takayuki Hoshino Sho Shimohama Natsumi Suzuki Ayaka Morimoto Azusa Oosumi Yuka Hoshino Kenji Tai Hirofumi Aoyagi Yoshiaki Sato Junro Kuromitsu Jin Nakahara Masaru Mimura Daisuke Ito |
| author_facet | Masahito Kubota Shogyoku Bun Keisuke Takahata Shin Kurose Yuki Momota Yu Iwabuchi Toshiki Tezuka Hajime Tabuchi Morinobu Seki Yasuharu Yamamoto Ryo Shikimoto Yu Mimura Takayuki Hoshino Sho Shimohama Natsumi Suzuki Ayaka Morimoto Azusa Oosumi Yuka Hoshino Kenji Tai Hirofumi Aoyagi Yoshiaki Sato Junro Kuromitsu Jin Nakahara Masaru Mimura Daisuke Ito |
| author_sort | Masahito Kubota |
| collection | DOAJ |
| description | Abstract Background Plasma biomarkers offer a promising alternative to amyloid beta (Aβ) positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers for diagnosing Alzheimer’s disease (AD). This cross-sectional study assessed the utility of multiple plasma biomarkers for diagnosing and staging AD in a Japanese cohort. Methods The assessed plasma biomarkers included Aβ42/40, phosphorylated tau (p-tau181 and p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), individually and in combination. Aβ42/40 was measured using the HISCL® platform, while all other biomarkers were measured using the Simoa® platform. Participants were classified based on Aβ PET imaging and neuropsychological testing into healthy controls (HC), AD continuum (preclinical AD, mild cognitive impairment [AD-MCI], and mild dementia [AD-D]), and non-AD cognitive impairment (CI) groups. Receiver operating characteristic analyses were performed to predict the Aβ PET status, correlation with Centiloid (CL) values and cognitive scores, and biomarker comparisons across AD stages. Results Sixty-nine HC, 13 preclinical AD, 38 AD-MCI, 44 AD-D, and 79 non-AD CI participants were included. The area under the curves (AUCs) for predicting Aβ PET status were 0.937 (Aβ42/40), 0.926 (p-tau217), and 0.946 (p-tau217/Aβ42); results of pair-wise DeLong tests revealed no significant differences among these three metrics (all p > 0.05). In the cognitively normal group, the AUCs were 0.968 (Aβ42/40), 0.958 (p-tau217), and 0.979 (p-tau217/Aβ42), while in the cognitively impaired group, they were 0.919 (Aβ42/40), 0.893 (p-tau217), and 0.923 (p-tau217/Aβ42). Among HC and AD continuum participants, CL correlations were − 0.74 (Aβ42/40), 0.81 (p-tau217), and 0.83 (p-tau217/Aβ42). In the HC and AD continuum, Aβ42/40 levels showed a bimodal distribution (cutoff = 0.096), with a shift from high to low occurring at 19.3 CL, compared to the PET positivity threshold of 32.9 CL. P-tau217 exhibited a linear increase with disease progression. All biomarkers correlated strongly with logical memory scores. Conclusions Plasma biomarkers, Aβ42/40 and p-tau217, and particularly their ratio (p-tau217/Aβ42), show strong potential as Aβ PET alternatives for AD diagnosis. HISCL-based plasma Aβ42/40 detects Aβ accumulation earlier than Aβ PET visual reading threshold, underscoring its utility as an early diagnostic marker. |
| format | Article |
| id | doaj-art-d1fb2db857a84ba8ac82a97156d8ccff |
| institution | OA Journals |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-d1fb2db857a84ba8ac82a97156d8ccff2025-08-20T02:30:45ZengBMCAlzheimer’s Research & Therapy1758-91932025-06-0117111210.1186/s13195-025-01778-8Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohortMasahito Kubota0Shogyoku Bun1Keisuke Takahata2Shin Kurose3Yuki Momota4Yu Iwabuchi5Toshiki Tezuka6Hajime Tabuchi7Morinobu Seki8Yasuharu Yamamoto9Ryo Shikimoto10Yu Mimura11Takayuki Hoshino12Sho Shimohama13Natsumi Suzuki14Ayaka Morimoto15Azusa Oosumi16Yuka Hoshino17Kenji Tai18Hirofumi Aoyagi19Yoshiaki Sato20Junro Kuromitsu21Jin Nakahara22Masaru Mimura23Daisuke Ito24Department of Neurology, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Radiology, Keio University School of MedicineDepartment of Neurology, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neurology, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neurology, Keio University School of MedicineDepartment of Neurology, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neurology, Keio University School of MedicineEisai-Keio Innovation Laboratory for Dementia, DCV Function, DHBL, Eisai Co., LtdEisai-Keio Innovation Laboratory for Dementia, DCV Function, DHBL, Eisai Co., LtdEisai-Keio Innovation Laboratory for Dementia, DCV Function, DHBL, Eisai Co., LtdEisai-Keio Innovation Laboratory for Dementia, DCV Function, DHBL, Eisai Co., LtdDepartment of Neurology, Keio University School of MedicineDepartment of Neuropsychiatry, Keio University School of MedicineDepartment of Neurology, Keio University School of MedicineAbstract Background Plasma biomarkers offer a promising alternative to amyloid beta (Aβ) positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers for diagnosing Alzheimer’s disease (AD). This cross-sectional study assessed the utility of multiple plasma biomarkers for diagnosing and staging AD in a Japanese cohort. Methods The assessed plasma biomarkers included Aβ42/40, phosphorylated tau (p-tau181 and p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), individually and in combination. Aβ42/40 was measured using the HISCL® platform, while all other biomarkers were measured using the Simoa® platform. Participants were classified based on Aβ PET imaging and neuropsychological testing into healthy controls (HC), AD continuum (preclinical AD, mild cognitive impairment [AD-MCI], and mild dementia [AD-D]), and non-AD cognitive impairment (CI) groups. Receiver operating characteristic analyses were performed to predict the Aβ PET status, correlation with Centiloid (CL) values and cognitive scores, and biomarker comparisons across AD stages. Results Sixty-nine HC, 13 preclinical AD, 38 AD-MCI, 44 AD-D, and 79 non-AD CI participants were included. The area under the curves (AUCs) for predicting Aβ PET status were 0.937 (Aβ42/40), 0.926 (p-tau217), and 0.946 (p-tau217/Aβ42); results of pair-wise DeLong tests revealed no significant differences among these three metrics (all p > 0.05). In the cognitively normal group, the AUCs were 0.968 (Aβ42/40), 0.958 (p-tau217), and 0.979 (p-tau217/Aβ42), while in the cognitively impaired group, they were 0.919 (Aβ42/40), 0.893 (p-tau217), and 0.923 (p-tau217/Aβ42). Among HC and AD continuum participants, CL correlations were − 0.74 (Aβ42/40), 0.81 (p-tau217), and 0.83 (p-tau217/Aβ42). In the HC and AD continuum, Aβ42/40 levels showed a bimodal distribution (cutoff = 0.096), with a shift from high to low occurring at 19.3 CL, compared to the PET positivity threshold of 32.9 CL. P-tau217 exhibited a linear increase with disease progression. All biomarkers correlated strongly with logical memory scores. Conclusions Plasma biomarkers, Aβ42/40 and p-tau217, and particularly their ratio (p-tau217/Aβ42), show strong potential as Aβ PET alternatives for AD diagnosis. HISCL-based plasma Aβ42/40 detects Aβ accumulation earlier than Aβ PET visual reading threshold, underscoring its utility as an early diagnostic marker.https://doi.org/10.1186/s13195-025-01778-8Alzheimer’s diseasePlasma biomarkersAβ42/40p-tau217p-tau217/Aβ42HISCL |
| spellingShingle | Masahito Kubota Shogyoku Bun Keisuke Takahata Shin Kurose Yuki Momota Yu Iwabuchi Toshiki Tezuka Hajime Tabuchi Morinobu Seki Yasuharu Yamamoto Ryo Shikimoto Yu Mimura Takayuki Hoshino Sho Shimohama Natsumi Suzuki Ayaka Morimoto Azusa Oosumi Yuka Hoshino Kenji Tai Hirofumi Aoyagi Yoshiaki Sato Junro Kuromitsu Jin Nakahara Masaru Mimura Daisuke Ito Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort Alzheimer’s Research & Therapy Alzheimer’s disease Plasma biomarkers Aβ42/40 p-tau217 p-tau217/Aβ42 HISCL |
| title | Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort |
| title_full | Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort |
| title_fullStr | Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort |
| title_full_unstemmed | Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort |
| title_short | Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort |
| title_sort | plasma biomarkers for early detection of alzheimer s disease a cross sectional study in a japanese cohort |
| topic | Alzheimer’s disease Plasma biomarkers Aβ42/40 p-tau217 p-tau217/Aβ42 HISCL |
| url | https://doi.org/10.1186/s13195-025-01778-8 |
| work_keys_str_mv | AT masahitokubota plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT shogyokubun plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT keisuketakahata plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT shinkurose plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT yukimomota plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT yuiwabuchi plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT toshikitezuka plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT hajimetabuchi plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT morinobuseki plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT yasuharuyamamoto plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT ryoshikimoto plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT yumimura plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT takayukihoshino plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT shoshimohama plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT natsumisuzuki plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT ayakamorimoto plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT azusaoosumi plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT yukahoshino plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT kenjitai plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT hirofumiaoyagi plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT yoshiakisato plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT junrokuromitsu plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT jinnakahara plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT masarumimura plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort AT daisukeito plasmabiomarkersforearlydetectionofalzheimersdiseaseacrosssectionalstudyinajapanesecohort |