Plasma phosphorylated tau217 has been suggested as a core biomarker for establishing biological Alzheimer's disease diagnosis. This blood biomarker has not been studied together with scalable cognitive assessment tools in population-based samples. We investigated the prevalence of cognitive and Alzheimer's disease biomarker abnormality and associations between plasma phosphorylated tau217 and remotely measured cognitive function in individuals without dementia. We used a population-based cross-sectional sample of 65-85-year-olds (n=692, 57% females) excluding those with previously diagnosed Alzheimer's disease or other dementia-causing neurodegenerative disease. Cognition was measured with telephone-administered word list recall task (episodic memory) and animal naming (semantic fluency). Plasma phosphorylated tau217 was determined with the ALZpath assay. The prevalence of individuals with abnormalities in tests measuring episodic memory, semantic fluency and plasma phosphorylated tau217 was 10-13%. Higher plasma phosphorylated tau217 was related to lower scores in telephone-administered cognitive tests. We found a substantial minority of a population-based sample of individuals without a clinical diagnosis of Alzheimer's disease to have cognitive and plasma phosphorylated tau217 profiles suggesting underlying Alzheimer's disease. Combining plasma phosphorylated tau217 with remote cognitive assessment could be a scalable, accessible, and cost-effective protocol for screening individuals with undiagnosed or risk for Alzheimer's disease.

A.P. is the Chief Scientific Officer of the FinnGen project, which is funded by 14 pharmaceutical companies. The FinnGen partner pharma companies are the following: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis Pharma AG, Boehringer Ingelheim International GmbH, and Bayer. H.R. is a current employee of Insitro Inc., and a former employee of Biogen.

doi:10.1136/bmjopen-2023-081947

This work was supported by the Sigrid Jusélius Foundation Senior Fellowship grant to Eero Vuoksimaa. TWINGEN study was funded by the FinnGen project that is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie, AstraZeneca UK, Biogen, Bristol Myers Squibb (and Celgene Corporation & Celgene International II), Genentech, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, GlaxoSmithKline Intellectual Property Development, Sanofi US Services, Maze Therapeutics, Janssen Biotech, Novartis, and Boehringer Ingelheim. Jaakko Kaprio acknowledges support by Academy of Finland Center of Excellence in Complex Disease Genetics (grant # 352792).

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TWINGEN study (704 participants) has ethical approval from the Helsinki and Uusimaa hospital district (HUS) Regional Committee on Medical Research Ethics (approval number 16831/2022). In addition, permission to recontact sample donors through the biobank was granted from THL Biobank (diary ID 83/2022). All participants provided written informed consent.

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