ArticleNeuropathology and applied neurobiology2015
A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort.
Article in Neuropathology and applied neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Senescence Markers and Associated Transcriptomic Changes Are Expressed at Early Stages of Alzheimer's Neuropathology but Are Not Independently Related to Dementia.International journal of molecular sciences · 2026Article
- Exercise alone or combined with functional foods in aging and age-related diseases: targeting DNA damage, repair pathways, and genome integrity.Frontiers in aging neuroscience · 2026Review
- Telomeric DNA damage response mediates neurotoxicity of Aβ42 oligomers in Alzheimer's disease.The EMBO journal · 2025Article
- Investigation into the Neuroprotective and Therapeutic Potential of Plant-Derived Chk2 Inhibitors.International journal of molecular sciences · 2024Review
- Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer's pathology and dementia in the CFAS population-derived neuropathology cohort.Neuroscience research · 2024Article
- Impact of double-strand breaks induced by uv radiation on neuroinflammation and neurodegenerative disorders.Molecular biology reports · 2024Review
- DLK-MAPK Signaling Coupled with DNA Damage Promotes Intrinsic Neurotoxicity Associated with Non-Mutated Tau.Molecular neurobiology · 2024Article
- Insights into the pathological basis of dementia from population-based neuropathology studies.Neuropathology and applied neurobiology · 2023Review
- Ageing in the brain: mechanisms and rejuvenating strategies.Cellular and molecular life sciences : CMLS · 2023Review
- Sting and p53 DNA repair pathways are compromised in Alzheimer's disease.Scientific reports · 2023Article
- Vibrotactile stimulation at gamma frequency mitigates pathology related to neurodegeneration and improves motor function.Frontiers in aging neuroscience · 2023Article
- Review
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives.Frontiers in aging neuroscience · 2021Review
- Breast cancer type 1 and neurodegeneration: consequences of deficient DNA repair.Brain communications · 2021Review
- P53 aggregation, interactions with tau, and impaired DNA damage response in Alzheimer's disease.Acta neuropathologica communications · 2020Article
- Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development.Aging and disease · 2020Review
- Expression of p16 and p21 in the frontal association cortex of ALS/MND brains suggests neuronal cell cycle dysregulation and astrocyte senescence in early stages of the disease.Neuropathology and applied neurobiology · 2020Article
- Identification of age- and gender-associated long noncoding RNAs in the human brain with Alzheimer's disease.Neurobiology of aging · 2019Article
- Early neuronal accumulation of DNA double strand breaks in Alzheimer's disease.Acta neuropathologica communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
aimsPopulation-based studies have shown that approximately 20% of the ageing population (aged 65 years and over) with dementia have little or no classical Alzheimer-type neuropathology. Cumulative DNA damage and a reduced capacity of DNA repair may result in neuronal dysfunction and contribute to cognitive impairment independent of Alzheimer-type pathology in the ageing brain.
methodsWe investigated expression of the DNA damage response (DDR)-associated molecules γH2AX and DNA-PKcs using immunohistochemistry and western blotting, and senescence-associated β-galactosidase in the frontal association neocortex of cases with low levels of Alzheimer-type pathology (Braak & Braak stage 0-II), and explored their relationship to cognitive impairment in a population-representative sample from the Medical Research Council's Cognitive Function and Ageing Study cohort.
resultsIncreases in both γH2AX(+) (r(s) = -0.36, P = 0.025) and DNA-PKcs(+) (r(s) = -0.39, P = 0.01) neuronal counts were associated with a lower Mini-Mental State Examination score. Increasing levels of senescence associated-β-gal(+) pyramidal neurones were weakly associated with the total number of DNA-PKcs(+) neurones (P = 0.08), but not with traditional senescence-associated signalling molecules, including p53 and p16.
conclusionThe association between the neuronal DDR and cognitive impairment, independent of AD pathology in the ageing brain, may be suggestive of a causal link via neuronal dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.