Plasma Aβ ratios in autosomal dominant Alzheimer’s disease: the influence of genotype
Abstract In-vitrostudies of autosomal dominant Alzheimer’s disease (ADAD) implicate longer Aβ peptides in pathogenesis, however less is known about the behaviour of ADAD mutationsin-vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from ADAD family members who were at-risk of inheriting a mutation or were already symptomatic. We tested for differences in plasma Aβ42:38, 38:40 and 42:40 ratios betweenPresenilin1 (PSEN1)andAmyloid Precursor Protein (APP)carriers. We examined the relationship between plasma andin-vitromodels of Aβ processing and, amongPSEN1carriers, tested for associations with parental age at onset (AAO). 39 participants were mutation carriers (28PSEN1and 11APP).Age- and sex-adjusted models showed marked differences in plasma Aβ betweenAPPandPSEN1: higher Aβ42:38 inPSEN1versusAPP(p<0.001) and non-carriers (p<0.001); higher Aβ38:40 inAPPversusPSEN1(p<0.001) and non-carriers (p<0.001), while Aβ42:40 was higher inAPPandPSEN1compared to non-carriers (both p<0.001). Aβ profiles were reasonably consistent in plasma and cell lines. WithinPSEN1, sex-adjusted models demonstrated negative associations between (i)Aβ42:40 (ii)Aβ42:38 and parental AAO.In-vivodifferences in Aβ processing betweenAPPandPSEN1provide insights into ADAD pathophysiology which can inform therapy development..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 17. Dez. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
O’Connor, Antoinette [VerfasserIn] |
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| doi: |
10.1101/2021.02.11.430756 |
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| PPN (Katalog-ID): |
XBI019933991 |
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| 245 | 1 | 0 | |a Plasma Aβ ratios in autosomal dominant Alzheimer’s disease: the influence of genotype |
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| 520 | |a Abstract In-vitrostudies of autosomal dominant Alzheimer’s disease (ADAD) implicate longer Aβ peptides in pathogenesis, however less is known about the behaviour of ADAD mutationsin-vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from ADAD family members who were at-risk of inheriting a mutation or were already symptomatic. We tested for differences in plasma Aβ42:38, 38:40 and 42:40 ratios betweenPresenilin1 (PSEN1)andAmyloid Precursor Protein (APP)carriers. We examined the relationship between plasma andin-vitromodels of Aβ processing and, amongPSEN1carriers, tested for associations with parental age at onset (AAO). 39 participants were mutation carriers (28PSEN1and 11APP).Age- and sex-adjusted models showed marked differences in plasma Aβ betweenAPPandPSEN1: higher Aβ42:38 inPSEN1versusAPP(p<0.001) and non-carriers (p<0.001); higher Aβ38:40 inAPPversusPSEN1(p<0.001) and non-carriers (p<0.001), while Aβ42:40 was higher inAPPandPSEN1compared to non-carriers (both p<0.001). Aβ profiles were reasonably consistent in plasma and cell lines. WithinPSEN1, sex-adjusted models demonstrated negative associations between (i)Aβ42:40 (ii)Aβ42:38 and parental AAO.In-vivodifferences in Aβ processing betweenAPPandPSEN1provide insights into ADAD pathophysiology which can inform therapy development. | ||
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| 700 | 1 | |a Arber, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Portelius, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Swift, Imogen |e verfasserin |4 aut | |
| 700 | 1 | |a Heslegrave, Amanda J |e verfasserin |4 aut | |
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