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Hultdin, Magnus
Publications (10 of 39) Show all publications
Carlund, O., Norberg, A., Osterman, P., Landfors, M., Degerman, S. & Hultdin, M. (2023). DNA methylation variations and epigenetic aging in telomere biology disorders. Scientific Reports, 13(1), Article ID 7955.
Open this publication in new window or tab >>DNA methylation variations and epigenetic aging in telomere biology disorders
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 7955Article in journal (Refereed) Published
Abstract [en]

Telomere Biology Disorders (TBDs) are characterized by mutations in telomere-related genes leading to short telomeres and premature aging but with no strict correlation between telomere length and disease severity. Epigenetic alterations are also markers of aging and we aimed to evaluate whether DNA methylation (DNAm) could be part of the pathogenesis of TBDs. In blood from 35 TBD cases, genome-wide DNAm were analyzed and the cases were grouped based on relative telomere length (RTL): short (S), with RTL close to normal controls, and extremely short (ES). TBD cases had increased epigenetic age and DNAm alterations were most prominent in the ES-RTL group. Thus, the differentially methylated (DM) CpG sites could be markers of short telomeres but could also be one of the mechanisms contributing to disease phenotype since DNAm alterations were observed in symptomatic, but not asymptomatic, cases with S-RTL. Furthermore, two or more DM-CpGs were identified in four genes previously linked to TBD or telomere length (PRDM8, SMC4, VARS, and WNT6) and in three genes that were novel in telomere biology (MAS1L, NAV2, and TM4FS1). The DM-CpGs in these genes could be markers of aging in hematological cells, but they could also be of relevance for the progression of TBD.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-209273 (URN)10.1038/s41598-023-34922-1 (DOI)000992335400030 ()37193737 (PubMedID)2-s2.0-85159474361 (Scopus ID)
Funder
The Kempe FoundationsCancerforskningsfonden i NorrlandUmeå UniversityRegion Västerbotten
Available from: 2023-06-08 Created: 2023-06-08 Last updated: 2023-09-05Bibliographically approved
Kolijn, P. M., Späth, F., Khouja, M., Hengeveld, P. J., van der Straten, L., Darzentas, N., . . . Langerak, A. W. (2023). Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis [Letter to the editor]. Blood, 142(16), 1399-1403
Open this publication in new window or tab >>Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis
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2023 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 142, no 16, p. 1399-1403Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-213399 (URN)10.1182/blood.2023019609 (DOI)001098039300001 ()37523714 (PubMedID)2-s2.0-85168011461 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2023-08-31 Created: 2023-08-31 Last updated: 2023-12-20Bibliographically approved
Schäfer Hackenhaar, F., Josefsson, M., Nordin Adolfsson, A., Landfors, M., Kauppi, K., Porter, T., . . . the Australian Imaging Biomarkers and Lifestyle Study, . (2023). Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease. Journal of Alzheimer's Disease, 94(4), 1443-1464
Open this publication in new window or tab >>Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease
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2023 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 94, no 4, p. 1443-1464Article in journal (Refereed) Published
Abstract [en]

Background: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, hasshown promise for Alzheimer’s disease (AD) prediction.Objective: Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA)measures and identifying novel early blood-based DNAm AD-prediction biomarkers.

Methods: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models(LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16years before clinical onset, and post-onset follow-up. NovelDNAmbiomarkers were generated with epigenome-wide LMMs,and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10–16 years), and post-AD-onset time-points.

Results: EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkersshowed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions(p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOE 4-carriership(OR = 1.38 per 1 SD DNAmscore increase versus OR= 13.58 for 4-allele carriage; AUCs = 77.2% versus 87.0%). Literaturereview showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with ouridentified CpGs.

Conclusion: The limited predictive value of EAA for AD extends prior findings by considering a longer follow-up time, andwith appropriate control for age, sex, APOE, and blood-cell proportions. Results also highlight challenges with replicatingdiscriminatory or predictive CpGs across studies.

Place, publisher, year, edition, pages
IOS Press, 2023
Keywords
Alzheimer’s disease, biomarkers, DNA methylation, epigenomics, longitudinal studies
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:umu:diva-214007 (URN)10.3233/jad-230039 (DOI)37393498 (PubMedID)2-s2.0-85168428453 (Scopus ID)
Funder
Swedish Research Council, 2018-01729The Kempe Foundations, JCK-1922.1
Available from: 2023-09-02 Created: 2023-09-02 Last updated: 2024-04-08Bibliographically approved
Kolijn, P. M., Hosnijeh, F. S., Späth, F., Hengeveld, P. J., Agathangelidis, A., Saleh, M., . . . Langerak, A. W. (2022). High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis. Blood, 139(10), 1557-1563
Open this publication in new window or tab >>High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis
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2022 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 139, no 10, p. 1557-1563Article in journal (Refereed) Published
Abstract [en]

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.

Place, publisher, year, edition, pages
American Society of Hematology, 2022
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-203104 (URN)10.1182/blood.2021012890 (DOI)000769559500017 ()34662377 (PubMedID)2-s2.0-85122045401 (Scopus ID)
Funder
Region VästerbottenRegion SkåneSwedish Cancer SocietyEuropean CommissionNordForskSwedish Research CouncilEuropean Regional Development Fund (ERDF), PI13/00061European Regional Development Fund (ERDF), PI13/01162European Regional Development Fund (ERDF), PI14/01219European Regional Development Fund (ERDF), PI17/01280
Available from: 2023-01-16 Created: 2023-01-16 Last updated: 2023-01-16Bibliographically approved
Framme, J. L., Lundqvist, C., Lundell, A.-C., van Schouwenburg, P. A., Lemarquis, A. L., Thörn, K., . . . Ekwall, O. (2022). Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs. Journal of Clinical Immunology, 42, 618-633
Open this publication in new window or tab >>Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs
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2022 (English)In: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 42, p. 618-633Article in journal (Refereed) Published
Abstract [en]

Background: Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS).

Purpose: To investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS.

Methods: Subjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed.

Results: At follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells.

Conclusions: This long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.

Clinical Implications: This study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
22q11.2 deletion syndrome, DiGeorge syndrome, long-term outcome, newborn screening, severe combined immunodeficiency, T lymphopenia, TREC
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-192261 (URN)10.1007/s10875-021-01201-5 (DOI)000749126700001 ()35080750 (PubMedID)2-s2.0-85123620385 (Scopus ID)
Funder
Swedish Research Council, 2018-02752Cancerforskningsfonden i Norrland, AMP 20-1000
Available from: 2022-03-11 Created: 2022-03-11 Last updated: 2022-07-12Bibliographically approved
Bovinder Ylitalo, E., Thysell, E., Landfors, M., Brattsand, M., Jernberg, E., Crnalic, S., . . . Wikström, P. (2021). A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer. Clinical Epigenetics, 13(1), Article ID 133.
Open this publication in new window or tab >>A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer
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2021 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 13, no 1, article id 133Article in journal (Refereed) Published
Abstract [en]

Background: Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity.

Materials and methods: Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity.

Results: Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT.

Conclusions: A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

Place, publisher, year, edition, pages
BioMed Central, 2021
Keywords
Androgen receptor, DNA methylation, Gene expression, MetA, Metastasis, MetB, MetC, Prognosis, Prostate cancer, Subtypes
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-185893 (URN)10.1186/s13148-021-01119-0 (DOI)000670704300001 ()34193246 (PubMedID)2-s2.0-85109041809 (Scopus ID)
Available from: 2021-07-12 Created: 2021-07-12 Last updated: 2023-09-05Bibliographically approved
Patthey, A., Boman, K., Tavelin, B., Lindquist, D., Lundin, E. & Hultdin, M. (2021). Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma. Acta Oncologica, 60(9), 1218-1224
Open this publication in new window or tab >>Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma
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2021 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 60, no 9, p. 1218-1224Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.

MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.

RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).

CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2021
Keywords
Endometrioid Endometrial Carcinoma, Ploidy, Prognosis, S-phase fraction
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-185073 (URN)10.1080/0284186X.2021.1939146 (DOI)000665673800001 ()34156893 (PubMedID)2-s2.0-85108629114 (Scopus ID)
Funder
Region Västerbotten
Available from: 2021-06-23 Created: 2021-06-23 Last updated: 2023-03-24Bibliographically approved
Dernstedt, A., Leidig, J., Holm, A., Kerkman, P., Mjösberg, J., Ahlm, C., . . . Forsell, M. N. E. (2021). Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis. Frontiers in Immunology, 11, Article ID 599647.
Open this publication in new window or tab >>Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis
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2021 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 11, article id 599647Article in journal (Refereed) Published
Abstract [en]

Germinal centers (GC) are sites for extensive B cell proliferation and homeostasis is maintained by programmed cell death. The complement regulatory protein Decay Accelerating Factor (DAF) blocks complement deposition on host cells and therefore also phagocytosis of cells. Here, we show that B cells downregulate DAF upon BCR engagement and that T cell-dependent stimuli preferentially led to activation of DAF(lo) B cells. Consistent with this, a majority of light and dark zone GC B cells were DAF(lo) and susceptible to complement-dependent phagocytosis, as compared with DAF(hi) GC B cells. We could also show that the DAF(hi) GC B cell subset had increased expression of the plasma cell marker Blimp-1. DAF expression was also modulated during B cell hematopoiesis in the human bone marrow. Collectively, our results reveal a novel role of DAF to pre-prime activated human B cells for phagocytosis prior to apoptosis.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
human B cell development, germinal center (GC), decay accelerating factor (DAF), complement-mediated phagocytosis, complement regulating proteins
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-179577 (URN)10.3389/fimmu.2020.599647 (DOI)000608470700001 ()33469456 (PubMedID)2-s2.0-85099651060 (Scopus ID)
Funder
NIH (National Institute of Health), U19AI142777-01Swedish Research Council, 2016-06598
Available from: 2021-02-04 Created: 2021-02-04 Last updated: 2024-01-17Bibliographically approved
Pudas, S., Josefsson, M., Nordin Adolfsson, A., Landfors, M., Kauppi, K., Veng-Taasti, L. M., . . . Degerman, S. (2021). Short leukocyte telomeres, but not telomere attrition rates, predict memory decline in the 20-year longitudinal Betula study. The journals of gerontology. Series A, Biological sciences and medical sciences, 76(6), 955-963
Open this publication in new window or tab >>Short leukocyte telomeres, but not telomere attrition rates, predict memory decline in the 20-year longitudinal Betula study
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2021 (English)In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 76, no 6, p. 955-963Article in journal (Refereed) Published
Abstract [en]

Leukocyte telomere length (LTL) is a proposed biomarker for aging-related disorders, including cognitive decline and dementia. Long-term longitudinal studies measuring intra-individual changes in both LTL and cognitive outcomes are scarce, precluding strong conclusions about a potential aging-related relationship between LTL shortening and cognitive decline. This study investigated associations between baseline levels and longitudinal changes in LTL and memory performance across an up to 20-year follow-up in 880 dementia-free participants from a population-based study (mean baseline age: 56.8 years, range: 40–80; 52% female). Shorter baseline LTL significantly predicted subsequent memory decline (r = .34, 95% confidence interval: 0.06, 0.82), controlling for age, sex, and other relevant covariates. No significant associations were however observed between intra-individual changes in LTL and memory, neither concurrently nor with a 5-year time-lag between LTL shortening and memory decline. These results support the notion of short LTL as a predictive factor for aging-related memory decline, but suggest that LTL dynamics in adulthood and older age may be less informative of cognitive outcomes in aging. Furthermore, the results highlight the importance of long-term longitudinal evaluation of outcomes in biomarker research.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
Cognitive aging, Leukocyte telomere length, Longitudinal, Memory, Population-based
National Category
Gerontology, specialising in Medical and Health Sciences Geriatrics Neurosciences
Research subject
medical behavioral science; Geriatrics; Psychology
Identifiers
urn:nbn:se:umu:diva-181484 (URN)10.1093/gerona/glaa322 (DOI)000659456700002 ()33367599 (PubMedID)2-s2.0-85107088699 (Scopus ID)
Funder
Swedish Research Council, 2018-01729Region Västerbotten, RV-735451, RV-453141, RV-225461
Available from: 2021-03-13 Created: 2021-03-13 Last updated: 2024-04-08Bibliographically approved
Schäfer Hackenhaar, F., Josefsson, M., Nordin Adolfsson, A., Landfors, M., Kauppi, K., Hultdin, M., . . . Pudas, S. (2021). Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers. Alzheimer's Research & Therapy, 13, Article ID 130.
Open this publication in new window or tab >>Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers
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2021 (English)In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 13, article id 130Article in journal (Refereed) Published
Abstract [en]

Background: Leukocyte telomere length (LTL) has been shown to predict Alzheimer’s disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor.

Methods: We analyzed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards.

Results: After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1–24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404–7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947–2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD.

Conclusions: Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2021
Keywords
Leukocyte telomere length, Dementia, Risk factors, Time-to-event analysis, Competing risks, Vascular dementia, Death
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-186769 (URN)10.1186/s13195-021-00871-y (DOI)000673978800001 ()34266503 (PubMedID)2-s2.0-85110170246 (Scopus ID)
Note

Correction: Hackenhaar, F.S., Josefsson, M., Adolfsson, A.N. et al. Correction: Short leukocyte telomeres predict 25-year Alzheimer’s disease incidence in non-APOE ε4-carriers. Alz Res Therapy 16, 39 (2024). DOI: 10.1186/s13195-024-01388-w

Available from: 2021-08-20 Created: 2021-08-20 Last updated: 2024-04-08Bibliographically approved
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