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APOE ϵ4 genotype-de...
APOE ϵ4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease
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Konijnenberg, E. (author)
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Tijms, B. M. (author)
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- Gobom, Johan (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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Dobricic, V. (author)
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Bos, I. (author)
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Vos, S. (author)
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Tsolaki, M. (author)
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Verhey, F. (author)
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- Popp, J. (author)
- Karolinska Institutet
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Martinez-Lage, P. (author)
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Vandenberghe, R. (author)
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Lleó, A. (author)
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Frölich, L. (author)
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Lovestone, S. (author)
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Streffer, J. (author)
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Bertram, L. (author)
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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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Teunissen, C. E. (author)
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Veerhuis, R. (author)
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Smit, A. B. (author)
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Scheltens, P. (author)
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- Zetterberg, Henrik, 1973 (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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Visser, P. J. (author)
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(creator_code:org_t)
- 2020-05-27
- 2020
- English.
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In: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
- Related links:
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https://alzres.biome...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background: Aggregation of amyloid β into plaques in the brain is one of the earliest pathological events in Alzheimer's disease (AD). The exact pathophysiology leading to dementia is still uncertain, but the apolipoprotein E (APOE) ϵ4 genotype plays a major role. We aimed to identify the molecular pathways associated with amyloid β aggregation using cerebrospinal fluid (CSF) proteomics and to study the potential modifying effects of APOE ϵ4 genotype. Methods: We tested 243 proteins and protein fragments in CSF comparing 193 subjects with AD across the cognitive spectrum (65% APOE ϵ4 carriers, average age 75 ± 7 years) against 60 controls with normal CSF amyloid β, normal cognition, and no APOE ϵ4 allele (average age 75 ± 6 years). Results: One hundred twenty-nine proteins (53%) were associated with aggregated amyloid β. APOE ϵ4 carriers with AD showed altered concentrations of proteins involved in the complement pathway and glycolysis when cognition was normal and lower concentrations of proteins involved in synapse structure and function when cognitive impairment was moderately severe. APOE ϵ4 non-carriers with AD showed lower expression of proteins involved in synapse structure and function when cognition was normal and lower concentrations of proteins that were associated with complement and other inflammatory processes when cognitive impairment was mild. Repeating analyses for 114 proteins that were available in an independent EMIF-AD MBD dataset (n = 275) showed that 80% of the proteins showed group differences in a similar direction, but overall, 28% effects reached statistical significance (ranging between 6 and 87% depending on the disease stage and genotype), suggesting variable reproducibility. Conclusions: These results imply that AD pathophysiology depends on APOE genotype and that treatment for AD may need to be tailored according to APOE genotype and severity of the cognitive impairment. © 2020 The Author(s).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Amyloid aggregation
- APOE genotype
- CSF proteomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Konijnenberg, E.
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Tijms, B. M.
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Gobom, Johan
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Dobricic, V.
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Bos, I.
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Vos, S.
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show more...
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Tsolaki, M.
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Verhey, F.
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Popp, J.
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Martinez-Lage, P ...
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Vandenberghe, R.
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Lleó, A.
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Frölich, L.
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Lovestone, S.
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Streffer, J.
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Bertram, L.
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Blennow, Kaj, 19 ...
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Teunissen, C. E.
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Veerhuis, R.
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Smit, A. B.
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Scheltens, P.
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Zetterberg, Henr ...
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Visser, P. J.
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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 Clinical Medicin ...
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and Psychiatry
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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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Alzheimer's Rese ...
- By the university
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University of Gothenburg
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Karolinska Institutet