Comparative Analysis of Different Definitions of Amyloid-beta Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer

• Amyloid-beta (A beta) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early A beta pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer'scontinuumis critical. Here, we compare different A beta classification approaches and we show their performance in detecting pathophysiological changes downstream A beta pathology. We studied 368 cognitively unimpaired individuals of the ALFA+ study, many of whom in the preclinical stage of the Alzheimer'scontinuum.Participants underwent A beta PET and CSF biomarkers assessment. We classified participants as A beta -positive using five approaches: (1) CSF A beta 42 < 1098 pg/ml; (2) CSF A beta 42/40 < 0.071; (3) A beta PET Centiloid > 12; (4) A beta PET Centiloid > 30 or (5) A beta PET Positive visual read. We assessed the correlations between A beta biomarkers and compared the prevalence of A beta positivity. We determined which approach significantly detected associations between A beta pathology and tau/neurodegeneration CSF biomarkers. We found that CSF-based approaches result in a higher A beta-positive prevalence than PET-based ones. There was a higher number of discordant participants classified as CSF A beta-positive but PET A beta-negative than CSF A beta-negative but PET A beta-positive. The CSF A beta 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the A beta-positive group. Altogether, we highlight the need for sensitive A beta -classifications to study the preclinical Alzheimer'scontinuumApproaches that define A beta positivity based on optimal discrimination of symptomatic Alzheimer's disease patients may be suboptimal for the detection of early pathophysiological alterations in preclinical Alzheimer.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

biomarkers

cerebrospinal fluid

positron emission

tomography

preclinical Alzheimer

aa research framework

biological definition

ratios

Neurosciences & Neurology

Publikations- och innehållstyp

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