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Preclinical effects...
Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations
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- Lautner, Ronald (author)
- Sahlgrenska Academy,Sahlgrenska University Hospital
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- Insel, Philip S. (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Skillbäck, Tobias (author)
- Sahlgrenska University Hospital,Sahlgrenska Academy
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- Olsson, Bob (author)
- Sahlgrenska University Hospital,Sahlgrenska Academy
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- Landén, Mikael (author)
- Karolinska Institutet,Karolinska Institute,Sahlgrenska Academy
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- Frisoni, Giovanni B (author)
- Centro San Giovanni di Dio Fatebenefratelli
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- Herukka, Sanna-Kaisa (author)
- University of Eastern Finland
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- Hampel, Harald (author)
- Pitié-Salpêtrière University Hospital
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- Wallin, Anders (author)
- Sahlgrenska Academy
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- Minthon, Lennart (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups,Skåne University Hospital
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- Blennow, Kaj (author)
- Sahlgrenska University Hospital,Sahlgrenska Academy
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- Mattsson, Niklas (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Zetterberg, Henrik (author)
- Sahlgrenska University Hospital,Sahlgrenska Academy
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(creator_code:org_t)
- 2017-10-23
- 2017
- English.
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In: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 9:1
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https://alzres.biome...
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Abstract
Subject headings
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- Background: From earlier studies it is known that the APOE ϵ2/ϵ3/ϵ4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aβ42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD. Methods: APOE genotype and CSF Aβ42 concentration were determined in a cohort comprising 716 cognitively healthy individuals aged 17-99 from nine different clinical research centers. Results: CSF concentrations of Aβ42 were lower in APOE ϵ4 carriers than in noncarriers in a gene dose-dependent manner. The effect of APOE ϵ4 on CSF Aβ42 was age dependent. The age at which CSF Aβ42 concentrations started to decrease was estimated at 50 years in APOE ϵ4-negative individuals and 43 years in heterozygous APOE ϵ4 carriers. Homozygous APOE ϵ4 carriers showed a steady decline in CSF Aβ42 concentrations with increasing age throughout the examined age span. Conclusions: People possessing the APOE ϵ4 allele start to show a decrease in CSF Aβ42 concentration almost a decade before APOE ϵ4 noncarriers already in early middle age. Homozygous APOE ϵ4 carriers might deposit Aβ42 throughout the examined age span. These results suggest that there is an APOE ϵ4-dependent period of early alterations in amyloid homeostasis, when amyloid slowly accumulates, that several years later, together with other downstream pathological events such as tau pathology, translates into cognitive decline.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Alzheimer's disease
- APOE
- Beta amyloid
- Cerebrospinal fluid
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Lautner, Ronald
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Insel, Philip S.
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Skillbäck, Tobia ...
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Olsson, Bob
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Landén, Mikael
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Frisoni, Giovann ...
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show more...
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Herukka, Sanna-K ...
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Hampel, Harald
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Wallin, Anders
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Minthon, Lennart
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Hansson, Oskar
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Blennow, Kaj
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Mattsson, Niklas
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Zetterberg, Henr ...
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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
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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 Neurology
- Articles in the publication
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Alzheimer's Rese ...
- By the university
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Lund University
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Karolinska Institutet