Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations

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Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations. / Lautner, Ronald; Insel, Philip S.; Skillbäck, Tobias; Olsson, Bob; Landén, Mikael; Frisoni, Giovanni B; Herukka, Sanna-Kaisa; Hampel, Harald; Wallin, Anders; Minthon, Lennart; Hansson, Oskar; Blennow, Kaj; Mattsson, Niklas; Zetterberg, Henrik.

I: Alzheimer's Research and Therapy, Vol. 9, Nr. 1, 87, 23.10.2017.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Lautner, R, Insel, PS, Skillbäck, T, Olsson, B, Landén, M, Frisoni, GB, Herukka, S-K, Hampel, H, Wallin, A, Minthon, L, Hansson, O, Blennow, K, Mattsson, N & Zetterberg, H 2017, 'Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations', Alzheimer's Research and Therapy, vol. 9, nr. 1, 87. https://doi.org/10.1186/s13195-017-0313-3

APA

Lautner, R., Insel, P. S., Skillbäck, T., Olsson, B., Landén, M., Frisoni, G. B., ... Zetterberg, H. (2017). Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations. Alzheimer's Research and Therapy, 9(1), [87]. https://doi.org/10.1186/s13195-017-0313-3

CBE

Lautner R, Insel PS, Skillbäck T, Olsson B, Landén M, Frisoni GB, Herukka S-K, Hampel H, Wallin A, Minthon L, Hansson O, Blennow K, Mattsson N, Zetterberg H. 2017. Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations. Alzheimer's Research and Therapy. 9(1). https://doi.org/10.1186/s13195-017-0313-3

MLA

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Author

Lautner, Ronald ; Insel, Philip S. ; Skillbäck, Tobias ; Olsson, Bob ; Landén, Mikael ; Frisoni, Giovanni B ; Herukka, Sanna-Kaisa ; Hampel, Harald ; Wallin, Anders ; Minthon, Lennart ; Hansson, Oskar ; Blennow, Kaj ; Mattsson, Niklas ; Zetterberg, Henrik. / Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations. I: Alzheimer's Research and Therapy. 2017 ; Vol. 9, Nr. 1.

RIS

TY - JOUR

T1 - Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations

AU - Lautner, Ronald

AU - Insel, Philip S.

AU - Skillbäck, Tobias

AU - Olsson, Bob

AU - Landén, Mikael

AU - Frisoni, Giovanni B

AU - Herukka, Sanna-Kaisa

AU - Hampel, Harald

AU - Wallin, Anders

AU - Minthon, Lennart

AU - Hansson, Oskar

AU - Blennow, Kaj

AU - Mattsson, Niklas

AU - Zetterberg, Henrik

PY - 2017/10/23

Y1 - 2017/10/23

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - APOE

KW - Beta amyloid

KW - Cerebrospinal fluid

UR - http://www.scopus.com/inward/record.url?scp=85032211993&partnerID=8YFLogxK

U2 - 10.1186/s13195-017-0313-3

DO - 10.1186/s13195-017-0313-3

M3 - Article

VL - 9

JO - Alzheimer's Research & Therapy

T2 - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

SN - 1758-9193

IS - 1

M1 - 87

ER -