Background: Although the usefulness of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) is well known, the use widely differs between countries. In Japan, measurement of phospho-tau181 (p-tau181) is covered by the national health care insurance from 2012 for differentiating the cause of dementia, and amyloidβ42/40 ratio was recently covered in 2023 only for evaluating eligibility for anti-Aβ antibodies. However, safety concerns and burden may have limited the use. We report the national trends of CSF AD biomarker testing in Japan. Methods: We used the open datasets of the national database from 2014 to 2023 that covers nearly all health insurance claims in Japan. Findings: The annual number of health insurance claims for p-tau181 gradually increased from 1,358 to 3,420. Claims were from in-patient settings in 79-86% throughout the period. The numbers of claims were highest in age group 75-79 and was higher in women in older age. Regional variances were identified. The number of claims for CSF Aβ42/40 ratio in the first 3 months from insurance coverage was 729 and 56% were from out-patient clinics. Interpretation: Although the numbers of CSF p-tau181 testing have gradually increased, the numbers were small compared to previous estimated annual diagnosis of AD. Tests were often performed in in-patient settings, and regional inequity existed. The coverage of CSF Aβ42/40 may have change some characteristics such as in- versus out-patient testing. These data may be important for simulation and cost estimation studies before the implementation of biomarker-based AD diagnosis in Japan and in other countries.

MK has received lecture fees from Eisai, Eli Lilly, and John Wiley & Sons; patent assignment fee from FUJIREBIO; and research support from Nihon Medi-Physics. RI has received advisory fees from Eli Lilly; and lecture fees from Eisai and Eli Lilly. KS's affiliation Dementia Inclusion and Therapeutics is an endorsed course funded by Effissimo Capital Management Pte Ltd. KS has nothing else to disclose. AI has received advisory fee from Eisai and Eli Lilly; stock ownership/capital gain from Eisai; lecture fees from Eisai, Eli Lilly, John Wiley & Sons, FUJIREBIO, HU Frontier, and Sysmex; and grants for commissioned/joint research from Eisai, Eli Lilly, FUJIREBIO, and Sysmex.

This study was supported by Integrated Research Initiative for Living Well with Dementia of Tokyo Metropolitan Institute for Geriatrics and Gerontology, and by Davos Alzheimer's Collaborative.

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national database (NDB) run by the Ministry of Health, Labour and Welfare of Japan (https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000177182.html)(in Japanese) e-Stat website (https://www.e-stat.go.jp/)

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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All data supporting the findings of this study is included in the manuscript or are available in NDB (in Japanese) or in e-Stat website.