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We analyzed plasma levels of A\u03b242 and A\u03b240 in a cohort of 719 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer\u2019s disease (AD) dementia and cognitively healthy elderly, using a ultrasensitive immunoassay (Simoa platform). There were weak positive correlations between plasma and cerebrospinal fluid (CSF) levels for both A\u03b242 and A\u03b240, and negative correlations between plasma A\u03b242 and neocortical amyloid deposition (measured with PET). Plasma levels of A\u03b242 and A\u03b240 were reduced in AD dementia compared with all other diagnostic groups. However, during the preclinical or prodromal AD stages (i.e. in amyloid positive controls, SCD and MCI) plasma concentration of A\u03b242 was just moderately decreased whereas A\u03b240 levels were unchanged. Higher plasma (but not CSF) levels of A\u03b2 were associated with white matter lesions, cerebral microbleeds, hypertension, diabetes and ischemic heart disease. In summary, plasma A\u03b2 is overtly decreased during the dementia stage of AD indicating that prominent changes in A\u03b2 metabolism occur later in the periphery compared to the brain. 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H.Z. and K.B. are co-founders of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. K.B. has served at Advisory Boards for IBL International, Roche Diagnostics, Eli Lilly and Amgen, and as a consultant for Novartis and Alzheon. A.J., L.S. and D.H. are employees of Quanterix Corporation. CATH is an employee of General Electric. D.B. is an employee of Janssen R&D.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26801"}}