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Age, sex and APOE-e...
Age, sex and APOE-epsilon 4 modify the balance between soluble and fibrillar beta-amyloid in non-demented individuals: topographical patterns across two independent cohorts
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-03-02
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Springer Science and Business Media LLC,2022
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/315254
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https://gup.ub.gu.se/publication/315254URI
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https://doi.org/10.1038/s41380-022-01436-7DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Amyloid (A beta) pathology is the earliest detectable pathophysiological event along the Alzheimer's continuum, which can be measured both in the cerebrospinal fluid (CSF) and by Positron Emission Tomography (PET). Yet, these biomarkers identify two distinct A beta pools, reflecting the clearance of soluble A beta as opposed to the presence of A beta fibrils in the brain. An open question is whether risk factors known to increase Alzheimer's' disease (AD) prevalence may promote an imbalance between soluble and deposited A beta. Unveiling such interactions shall aid our understanding of the biological pathways underlying A beta deposition and foster the design of effective prevention strategies. We assessed the impact of three major AD risk factors, such as age, APOE-epsilon 4 and female sex, on the association between CSF and PET A beta, in two independent samples of non-demented individuals (ALFA: n = 320, ADNI: n = 682). We tested our hypotheses both in candidate regions of interest and in the whole brain using voxel-wise non-parametric permutations. All of the assessed risk factors induced a higher A beta deposition for any given level of CSF A beta 42/40, although in distinct cerebral topologies. While age and sex mapped onto neocortical areas, the effect of APOE-epsilon 4 was prominent in the medial temporal lobe, which represents a target of early tau deposition. Further, we found that the effects of age and APOE-epsilon 4 was stronger in women than in men. Our data indicate that specific AD risk factors affect the spatial patterns of cerebral A beta aggregation, with APOE-epsilon 4 possibly facilitating a co-localization between A beta and tau along the disease continuum.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Salvado, G.
(author)
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Molinuevo, J. L.
(author)
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Shekari, M.
(author)
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Falcon, C.
(author)
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Operto, G.
(author)
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Suarez-Calvet, M.
(author)
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Mila-Aloma, M.
(author)
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Sala, A.
(author)
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Rodriguez-Vieitez, E.
(author)
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Kollmorgen, G.
(author)
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Suridjan, I.
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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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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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Gispert, J. D.
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
Related titles
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In:Molecular Psychiatry: Springer Science and Business Media LLC27, s. 2010-20181359-41841476-5578
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Cacciaglia, R.
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Salvado, G.
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Molinuevo, J. L.
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Shekari, M.
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Falcon, C.
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Operto, G.
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show more...
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Suarez-Calvet, M ...
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Mila-Aloma, M.
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Sala, A.
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Rodriguez-Vieite ...
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Kollmorgen, G.
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Suridjan, I.
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Gispert, J. D.
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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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Molecular Psychi ...
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University of Gothenburg