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Comparative Analysi...
Comparative Analysis of Different Definitions of Amyloid-beta Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer
- Article/chapterEnglish2021
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LIBRIS-ID:oai:gup.ub.gu.se/297735
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https://gup.ub.gu.se/publication/297735URI
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https://doi.org/10.14283/jpad.2020.51DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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Salvado, G.
(author)
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Shekari, M.
(author)
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Grau-Rivera, O.
(author)
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Sala-Vila, A.
(author)
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Sanchez-Benavides, G.
(author)
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Arenaza-Urquijo, E. M.
(author)
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Gonzalez-de-Echavarri, J. M.
(author)
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Simon, M.
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Kollmorgen, G.
(author)
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka
(author)
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Gispert, J. D.
(author)
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Suarez-Calvet, M.
(author)
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Molinuevo, J. L.
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Jpad-Journal of Prevention of Alzheimers Disease: SERDI8:1, s. 68-772274-5807
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Mila-Aloma, M.
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Salvado, G.
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Shekari, M.
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Grau-Rivera, O.
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Sala-Vila, A.
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Sanchez-Benavide ...
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Arenaza-Urquijo, ...
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Gonzalez-de-Echa ...
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Simon, M.
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Kollmorgen, G.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Gispert, J. D.
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Suarez-Calvet, M ...
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Molinuevo, J. L.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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University of Gothenburg