Observational and genetic studies of short telomeres and Alzheimer’s disease in 67,000 and 152,000 individuals: a Mendelian randomization study

Madrid, Alexander Scheller; Rasmussen, Katrine Laura; Rode, Line; Frikke‐Schmidt, Ruth; Nordestgaard, Børge G.; Bojesen, Stig E.

doi:10.1007/s10654-019-00563-w

Cited by 45 publications

(28 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus far, focus in the dementia field has been on shorter telomere length with studies finding observationally as well as genetically associations between shorter telomere length and increased risk of Alzheimer's disease [20][21][22][23]. Moreover, a recent meta-analysis which included 13 primary studies demonstrated significantly shorter telomere length in 860 Alzheimer's disease patients compared to 2,022 controls [8].…”

Section: Discussionmentioning

confidence: 99%

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Fani

Hilal

Sedaghat

et al. 2020

JAD

View full text Add to dashboard Cite

There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4 ± 9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population.

show abstract

Section: Discussionmentioning

confidence: 99%

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Fani

Hilal

Sedaghat

et al. 2020

JAD

View full text Add to dashboard Cite

show abstract

“…Telomere shortening leads to a permanent cell cycle arrest, which is known as replicative senescence. Numerous studies have shown that telomere shortening is associated with aging and aging-related diseases, including AD [59][60][61][62][63][64][65], although noassociation results have also been reported [66,67]. Lee et al reported that peripheral leukocyte DNA from individuals with AD has a greater telomere shortening rate per year than leukocytes from healthy individuals and individuals with mild cognitive impairment (MCI) [64].…”

Section: Evidence Of Cellular Senescence In Ad Patientsmentioning

confidence: 99%

“…Shortening of telomeres at the ends of mammalian chromosomes because of cellular replication leads to a permanent cell cycle arrest, which is also known as replicative senescence. Numerous studies have shown that telomere lengths are shorter in AD patients, compared with age-matched health controls [59][60][61][62][63][64][65], suggesting a potential role of telomere shortening in cell senescence in AD. The mechanism underlying telomere shortening in AD is unknown.…”

Section: Telomerase Deficiency and Telomere Shorteningmentioning

confidence: 99%

Aging, Cellular Senescence, and Alzheimer’s Disease

Liu

2022

IJMS

126

View full text Add to dashboard Cite

Aging is the greatest risk factor for late-onset Alzheimer’s disease (LOAD), which accounts for >95% of Alzheimer’s disease (AD) cases. The mechanism underlying the aging-related susceptibility to LOAD is unknown. Cellular senescence, a state of permanent cell growth arrest, is believed to contribute importantly to aging and aging-related diseases, including AD. Senescent astrocytes, microglia, endothelial cells, and neurons have been detected in the brain of AD patients and AD animal models. Removing senescent cells genetically or pharmacologically ameliorates β-amyloid (Aβ) peptide and tau-protein-induced neuropathologies, and improves memory in AD model mice, suggesting a pivotal role of cellular senescence in AD pathophysiology. Nonetheless, although accumulated evidence supports the role of cellular senescence in aging and AD, the mechanisms that promote cell senescence and how senescent cells contribute to AD neuropathophysiology remain largely unknown. This review summarizes recent advances in this field. We believe that the removal of senescent cells represents a promising approach toward the effective treatment of aging-related diseases, such as AD.

show abstract

“… Locus associated with mLOY? Associations between germline variation in gene and diseases of ageing Associations between somatic gene changes and diseases of ageing TERT Yes Yes Yes Cancer 164 ; CVD 165 – 167 ; dementia 178 Cancer 179 ; CVD 180 ; dementia 181 , 182 CHEK2 Yes Yes Yes Cancer 120 – 124 Cancer 183 ATM Yes Yes Yes Cancer 133 – 138 Cancer 184 TCL1A Yes Yes Yes NA Cancer 185 46/1 haplotype Yes Yes No Cancer 82 – 84 NA SH2B3 Yes Yes No Cancer 144 ; CVD 153 – 157 Cancer 144 TET2 Yes No Yes Cancer 141 – 143 ; CVD 148 Cancer 186 ; CVD 50 , 51 , 54 , 56 , 147 MAD1L1 …”

Section: Overlap With Processes Of Ageingmentioning

confidence: 99%

Germline risk of clonal haematopoiesis

2021

View full text Add to dashboard Cite

Clonal haematopoiesis (CH) is a common, age-related expansion of blood cells with somatic mutations that is associated with an increased risk of haematological malignancies, cardiovascular disease and all-cause mortality. CH may be caused by point mutations in genes associated with myeloid neoplasms, chromosomal copy number changes and loss of heterozygosity events. How inherited and environmental factors shape the incidence of CH is incompletely understood. Even though the several varieties of CH may have distinct phenotypic consequences, recent research points to an underlying genetic architecture that is highly overlapping. Moreover, there are numerous commonalities between the inherited variation associated with CH and that which has been linked to age-associated biomarkers and diseases. In this Review, we synthesize what is currently known about how inherited variation shapes the risk of CH and how this genetic architecture intersects with the biology of diseases that occur with ageing.

show abstract

Observational and genetic studies of short telomeres and Alzheimer’s disease in 67,000 and 152,000 individuals: a Mendelian randomization study

Cited by 45 publications

References 44 publications

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Aging, Cellular Senescence, and Alzheimer’s Disease

Germline risk of clonal haematopoiesis

Contact Info

Product

Resources

About