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- Xiao, Zhenxu, et al.
(författare)
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Olfactory function, neurofilament light chain, and cognitive trajectory : A 12-year follow-up of the Shanghai Aging Study
- 2023
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Ingår i: Alzheimer's and Dementia. - : John Wiley & Sons. - 2352-8729. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine whether blood neurofilament light chain (NfL) modifies the association of olfactory dysfunction (OD) with long-term cognitive decline. A total of 1125 non-demented older adults in the Shanghai Aging Study were evaluated for baseline olfaction (12-item Sniffin' Sticks Smell Test) and cognitive trajectory by a 12-year follow-up. Baseline blood NfL was quantified using Single Molecular Array assay, and dichotomized into low and high levels based on the median value of concentration. The Mini-Mental State Examination (MMSE) and Telephone Interview for Cognitive Status-40 were used to assess participants' cognitive function. Cognitive decline was ascertained when dementia was diagnosed or documented in the medical record during follow-up, or the MMSE declining rate (slope) was 1.0 SD larger than the group mean. OD participants presented a steeper trajectory of MMSE score (p interaction = 0.004) and a high risk of cognitive decline (adjusted HR [95% CI], 1.82 [1.11, 2.98]) only in those with high NfL. Participants with combined OD and high NfL showed the highest risk of cognitive decline (adjusted HR, 2.43 [1.20, 4.92]). OD, especially in combination with high blood NfL concentration, may be able to identify individuals who later incur cognitive deterioration.
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| 2. |
- Xiao, Zhenxu, et al.
(författare)
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Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort : The Shanghai Aging Study
- 2023
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Ingår i: Alzheimer's and Dementia. - : John Wiley & Sons. - 2352-8729. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community-based cohort was limited only in high-income countries.METHODS: This study included 1857 dementia-free community residents recruited in 2009-2011 and followed up in waves 2014-2016 and 2019-2023 in the Shanghai Aging Study. We intended to explore the relationships of baseline plasma ALZpath phosphorylated tau 217 (p-tau217), p-tau181, neurofilament light chain (NfL) with follow-up incident dementia, Alzheimer's disease (AD), and amyloidosis.RESULTS: Higher concentrations of plasma p-tau217, p-tau181, and NfL were correlated to higher decline speed of Mini-Mental State Examination score, and higher risk of incident dementia and AD. The p-tau217 demonstrated a significant correlation with longitudinal neocortical amyloid-beta (Aβ) deposition (r = 0.57 [0.30, 0.76]) and a high accuracy differentiating Aβ+ from Aβ- at follow-ups (area under the receiver operating characteristic curve = 0.821 [0.703, 0.940]).DISCUSSION: Plasma p-tau217 may be an early predictive marker of AD and Aβ pathology in older community-dwelling individuals.Highlights: Plasma p-tau217, p-tau181, and NfL were positively associated with long-term cognitive decline and risk of incident dementia.Plasma p-tau217 showed a better performance distinguishing Aβ+ individuals from Aβ- individuals at follow-ups.Plasma NfL may be a suitable predictor of general cognitive decline in older community-dwelling individuals.
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| 3. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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