Interactions between apolipoprotein E, sex, and amyloid-beta on cerebrospinal fluid p-tau levels in the European prevention of Alzheimer's dementia longitudinal cohort study (EPAD LCS)
| Autor: | Tyler S. Saunders, Natalie Jenkins, Kaj Blennow, Craig Ritchie, Graciela Muniz-Terrera |
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| Rok vydání: | 2022 |
| Předmět: |
Alzheimer Disease/diagnosis
Amyloid beta-Peptides Apolipoprotein E4 tau Proteins/cerebrospinal fluid tau Proteins General Medicine Peptide Fragments General Biochemistry Genetics and Molecular Biology Cohort Studies Apolipoproteins E Alzheimer Disease Humans Biomarkers/cerebrospinal fluid Female Longitudinal Studies Apolipoprotein E4/genetics Apolipoproteins E/genetics Biomarkers |
| Zdroj: | Saunders, T S, Jenkins, N, Blennow, K, Ritchie, C & Muniz-Terrera, G 2022, ' Interactions between apolipoprotein E, sex, and amyloid-beta on cerebrospinal fluid p-tau levels in the European prevention of Alzheimer's dementia longitudinal cohort study (EPAD LCS) ', EBioMedicine, vol. 83, 104241 . https://doi.org/10.1016/j.ebiom.2022.104241 |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2022.104241 |
| Popis: | BACKGROUND: Alzheimer's Disease, the leading cause of dementia, is over-represented in females. The apolipoprotein E (APOE)ε4 allele is the strongest genetic risk factor for late-onset AD and is associated with aberrant cerebrospinal fluid levels (CSF) of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ). There is some evidence that sex may mediate the relationship between APOE status and CSF tau, however, evidence is mixed.METHODS: We aimed to examine the interaction between sex, APOE ε4 status, CSF Aβ on t-tau and p-tau in 1599 mid-to-late life individuals without a diagnosis of dementia in the European Prevention of Alzheimer's Dementia (EPAD) longitudinal cohort study.FINDINGS: We found a significant interaction between APOE status, sex, and CSF Aβ on CSF p-tau levels (β = 0·18, p = 0·04). Specifically, there was a stronger association between APOE status and CSF Aβ 42 on CSF p-tau in males compared to females. Further, in females with high Aβ levels (reflecting less cortical deposition), ε4 carriers had significantly elevated p-tau levels relative to non-carriers (W = 39663, p = 0·01). However, there were no significant differences in p-tau between male ε4 carriers and non-carriers with high Aβ (W = 23523, p = 0·64). INTERPRETATION: An interaction between sex and cerebrospinal fluid Aβ may mediate the relationship between APOE status and CSF p-tau. These data suggest tau accumulation may be independent of Aβ in females, but not males.FUNDING: Innovative Medicines Initiative, Swedish Research Council, Alzheimer Drug Discovery Foundation, Swedish Alzheimer Foundation, the Swedish state under the agreement between the Swedish government and the County Councils: the ALF-agreement, and the Alzheimer's Association 2021 Zenith Award. |
| Databáze: | OpenAIRE |
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