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Cerebral Aβ deposit...
Cerebral Aβ deposition precedes reduced cerebrospinal fluid and serum Aβ42/Aβ40 ratios in the App NL−F/NL−F knock-in mouse model of Alzheimer’s disease
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- Andersson, Emelie (author)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Klinisk minnesforskning,Lund University Research Groups,Clinical Memory Research
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- Schultz, Nina (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Nationella forskarskolan om åldrande och hälsa,Clinical Memory Research,Lund University Research Groups,National Graduate School on Ageing and Health
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- Saito, Takashi (author)
- Nagoya City University
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- Saido, Takaomi C. (author)
- RIKEN Center for Brain Science
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- Blennow, Kaj (author)
- University of Gothenburg,Sahlgrenska University Hospital,Sahlgrenska Academy
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- Gouras, Gunnar K. (author)
- Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Experimental Dementia Research,Lund University Research Groups,Faculty of Medicine,LU Profile Area: Proactive Ageing,Lund University Profile areas
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- Zetterberg, Henrik (author)
- University of Gothenburg,Sahlgrenska Academy,Hong Kong Center for Neurodegenerative Diseases,University College London,Sahlgrenska University Hospital,University of Wisconsin-Madison
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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(creator_code:org_t)
- 2023-03-25
- 2023
- English.
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In: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1
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Abstract
Subject headings
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- Background: Aβ42/Aβ40 ratios in cerebrospinal fluid (CSF) and blood are reduced in preclinical Alzheimer’s disease (AD), but their temporal and correlative relationship with cerebral Aβ pathology at this early disease stage is not well understood. In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD. Methods: CSF, serum, and brain tissue were collected from 3- to 18-month-old AppNL−F/NL−F knock-in mice (n = 48) and 2–18-month-old AppNL/NL knock-in mice (n = 35). The concentrations of Aβ42 and Aβ40 in CSF and serum were measured using Single molecule array (Simoa) immunoassays. Cerebral Aβ plaque burden was assessed in brain tissue sections by immunohistochemistry and thioflavin S staining. Furthermore, the concentrations of Aβ42 in soluble and insoluble fractions prepared from cortical tissue homogenates were measured using an electrochemiluminescence immunoassay. Results: In AppNL−F/NL−F knock-in mice, Aβ42/Aβ40 ratios in CSF and serum were significantly reduced from 12 and 16 months of age, respectively. The initial reduction of these biomarkers coincided with cerebral Aβ pathology, in which a more widespread Aβ plaque burden and increased levels of Aβ42 in the brain were observed from approximately 12 months of age. Accordingly, in the whole study population, Aβ42/Aβ40 ratios in CSF and serum showed a negative hyperbolic association with cerebral Aβ plaque burden as well as the levels of both soluble and insoluble Aβ42 in the brain. These associations tended to be stronger for the measures in CSF compared with serum. In contrast, no alterations in the investigated fluid biomarkers or apparent cerebral Aβ plaque pathology were found in AppNL/NL knock-in mice during the observation time. Conclusions: Our findings suggest a temporal sequence of events in AppNL−F/NL−F knock-in mice, in which initial deposition of Aβ aggregates in the brain is followed by a decline of the Aβ42/Aβ40 ratio in CSF and serum once the cerebral Aβ pathology becomes significant. Our results also indicate that the investigated biomarkers were somewhat more strongly associated with measures of cerebral Aβ pathology when assessed in CSF compared with serum.
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
- Beta-amyloid
- Biomarker
- Blood
- Cerebrospinal fluid
Publication and Content Type
- art (subject category)
- ref (subject category)
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