Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults.

• The objective of this study was to evaluate novel plasma p-tau231 and p-tau181, as well as Aβ40 and Aβ42 assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults.In a cohort of 244 older adults at risk of Alzheimer's disease (AD) owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231 and p-tau181), Aβ40 and Aβ42 with immunoprecipitation mass spectrometry, and Simoa neurofilament light (NfL). A subset of 129 participants underwent amyloid-β (18 F-NAV4694) and tau (18 F-flortaucipir) PET assessments. We investigated plasma biomarker associations with Aβ and tau PET at the global and voxel level and tested plasma biomarker combinations for improved detection of Aβ-PET positivity. We also investigated associations with 8-year cognitive change.Plasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal, and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma Aβ42/40 explained more variance in global Aβ-PET binding than Aβ42 alone. P-tau231 also showed strong and widespread associations with cortical Aβ-PET binding. Combining Aβ42/40 with p-tau231 or p-tau181 allowed for good distinction between Aβ-negative and -positive participants (area under the receiver operating characteristic curve [AUC] range=0.81-0.86). Individuals with low plasma Aβ42/40 and high p-tau experienced faster cognitive decline.Plasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in presymptomatic individuals. The combination of p-tau and Aβ42/40 biomarkers detected early AD pathology and cognitive decline. Such markers could be used as prescreening tools to reduce the cost of prevention trials. ANN NEUROL 2022.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Geriatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Geriatrics (hsv//eng)

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