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APOE epsilon 4 gene...
APOE epsilon 4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly
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- Snellman, Anniina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Ekblad, L. L. (author)
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Tuisku, J. (author)
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Koivumaki, M. (author)
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- Ashton, Nicholas J. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Lantero Rodriguez, Juan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Karikari, Thomas (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Helin, S. (author)
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- Bucci, M. (author)
- Karolinska Institutet
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Loyttyniemi, E. (author)
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Parkkola, R. (author)
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Karrasch, M. (author)
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- Schöll, Michael, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Wallenberg Centre for Molecular and Translational Medicine,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Rinne, J. O. (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Alzheimers Research & Therapy. - 1758-9193. ; 15:1
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- BackgroundNeuroinflammation, characterized by increased reactivity of microglia and astrocytes in the brain, is known to be present at various stages of the Alzheimer's disease (AD) continuum. However, its presence and relationship with amyloid pathology in cognitively normal at-risk individuals is less clear. Here, we used positron emission tomography (PET) and blood biomarker measurements to examine differences in neuroinflammation and beta-amyloid (A beta) and their association in cognitively unimpaired homozygotes, heterozygotes, or non-carriers of the APOE epsilon 4 allele, the strongest genetic risk for sporadic AD.MethodsSixty 60-75-year-old APOE epsilon 4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) were recruited in collaboration with the local Auria biobank. The participants underwent C-11-PK11195 PET (targeting 18-kDa translocator protein, TSPO), C-11-PiB PET (targeting A beta), brain MRI, and neuropsychological testing including a preclinical cognitive composite (APCC). C-11-PK11195 distribution volume ratios and C-11-PiB standardized uptake value ratios (SUVRs) were calculated for regions typical for early A beta accumulation in AD. Blood samples were drawn for measuring plasma glial fibrillary acidic protein (GFAP) and plasma A beta(1-42/1.40).ResultsIn our cognitively unimpaired sample, cortical C-11-PiB-binding increased according to APOE epsilon 4 gene dose (median composite SUVR 1.47 (range 1.38-1.66) in non-carriers, 1.55 (1.43-2.02) in heterozygotes, and 2.13 (1.61-2.83) in homozygotes, P = 0.002). In contrast, cortical composite C-11-PK11195-binding did not differ between the APOE epsilon 4 gene doses (P = 0.27) or between A beta-positive and A beta-negative individuals (P = 0.81) and associated with higher A beta burden only in APOE epsilon 4 homozygotes (Rho = 0.47, P = 0.043). Plasma GFAP concentration correlated with cortical C-11-PiB (Rho = 0.35, P = 0.040), but not C-11-PK11195-binding (Rho = 0.13, P = 0.47) in A beta-positive individuals. In the total cognitively unimpaired population, both higher composite C-11-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, whereas elevated C-11-PiB-binding was associated with lower APCC scores.ConclusionsOnly A beta burden measured by PET, but not markers of neuroinflammation, differed among cognitively unimpaired elderly with different APOE epsilon 4 gene dose. However, APOE epsilon 4 gene dose seemed to modulate the association between neuroinflammation and A beta.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer's disease
- Microglia
- Astrocytes
- Beta-amyloid
- PET
- TSPO
- APOE
- Apolipoprotein E
- GFAP
- Biomarker
- microglial activation
- alzheimers-disease
- in-vivo
- translocator
- protein
- neuronal function
- burden
- association
- risk
- impairment
- deposition
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Snellman, Anniin ...
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Ekblad, L. L.
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Tuisku, J.
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Koivumaki, M.
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Ashton, Nicholas ...
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Lantero Rodrigue ...
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show more...
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Karikari, Thomas
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Helin, S.
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Bucci, M.
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Loyttyniemi, E.
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Parkkola, R.
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Karrasch, M.
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Schöll, Michael, ...
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Rinne, J. O.
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show less...
- About the subject
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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
- Articles in the publication
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Alzheimers Resea ...
- By the university
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University of Gothenburg
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Karolinska Institutet