Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

INTRODUCTION - Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS - We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8–11.5] years). RESULTS - General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION - These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia

ERCC1-deficient cells and mice are hypersensitive to lipid peroxidation

Lipid peroxidation (LPO) products are relatively stable and abundant metabolites, which accumulate in tissues of mammals with aging, being able to modify all cellular nucleophiles, creating protein and DNA adducts including crosslinks. Here, we used cells and mice deficient in the ERCC1-XPF endonuclease required for nucleotide excision repair and the repair of DNA interstrand crosslinks to ask if specifically LPO-induced DNA damage contributes to loss of cell and tissue homeostasis. Ercc1-/- mouse embryonic fibroblasts were more sensitive than wild-type (WT) cells to the LPO products: 4-hydroxy-2-nonenal (HNE), crotonaldehyde and malondialdehyde. ERCC1-XPF hypomorphic mice were hypersensitive to CCl4 and a diet rich in polyunsaturated fatty acids, two potent inducers of endogenous LPO. To gain insight into the mechanism of how LPO influences DNA repair-deficient cells, we measured the impact of the major endogenous LPO product, HNE, on WT and Ercc1-/- cells. HNE inhibited proliferation, stimulated ROS and LPO formation, induced DNA base damage, strand breaks, error-prone translesion DNA synthesis and cellular senescence much more potently in Ercc1-/- cells than in DNA repair-competent control cells. HNE also deregulated base excision repair and energy production pathways. Our observations that ERCC1-deficient cells and mice are hypersensitive to LPO implicates LPO-induced DNA damage in contributing to cellular demise and tissue degeneration, notably even when the source of LPO is dietary polyunsaturated fats

Speech‐in‐noise hearing impairment is associated with an increased risk of incident dementia in 82,039 UK Biobank participants

Introduction Little is known about the association between speech-in-noise (SiN) hearing impairment and dementia. Methods In 82,039 dementia-free participants aged ≥60 years were selected from the UK Biobank. Cox proportional-hazards models were used to investigate whether SiN hearing impairment is associated with an increased risk of incident dementia. Results Over 11 years of follow-up (median = 10.1), 1285 participants developed dementia. Insufficient and poor SiN hearing were associated with a 61% (hazard ratio [HR] = 1.61, 95% confidence [CI] 1.41–1.84) and 91% (HR = 1.91, 95% CI 1.55–2.36) increased risk of developing dementia, respectively, compared to normal SiN hearing. The association remained similar when restricting to follow-up intervals of ≤3, >3 to 6 to 9 years. There was limited evidence for mediation through depressive symptoms and social isolation. Discussion SiN hearing impairment is independently associated with incident dementia, providing further evidence for hearing impairment as a potential modifiable dementia risk factor

Intraspecific variability of yarrow (Achillea millefolium L. s.l.) in respect of developmental and chemical traits

The aim of study was to determine the variability of 20 yarrow populations introduced into ex situ conditions, in respect of selected developmental traits as well as content and composition of biologically active compounds (essential oil, tannins, flavonoids and phenolic acids). Field experiment was established at the Experimental Station, Department of Vegetable and Medicinal Plants. Morphological observations and harvest of raw material were carried out in the second year of plant vegetation, at the beginning of blooming. Investigated populations differed significantly in respect of developmental features as well as content and composition of identified compounds. The highest differences among the populations concerned fresh mass of herb (0.46–1.79 kg per plant), number of shoots per m2 (64–243) and length of the longest internode (42–158 mm). Total content of essential oil ranged from 0.10 to 1.00%. Among 24 identified compounds β-pinene, 1,8-cineole, terpinene-4-ol, nerolidol and chamazulene were the dominants. According to content of these compounds, three chemotypes were distinguished within investigated populations, i.e.: β-pinene, β-pinene + chamazulene and 1,8-cineole type. Content of tannins ranged from 0.38 to 0.90%. Four flavonoids were identified and apigenin 7-glucoside was present in the highest amount (from 9.87 to 475.21 mg × 100 g−1), while the highest differences between populations concerned the content of luteolin-3',7-diglucoside. Within phenolic acids, three compounds (caffeic acid derivatives) were identified. Rosmarinic acid was the dominant one (75.64–660.54 mg × 100 g−1), while cichoric acid differentiated investigated populations the most

Vitamin D and Memory Decline: Two Population-Based Prospective Studies

BACKGROUND: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. OBJECTIVE: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. METHODS: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. RESULTS: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). CONCLUSIONS: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.National Heart, Lung, and Blood Institute (NHLBI)National Institute of Neurological Disorders and Stroke (NINDS)National Institute on Aging (NIA)Alzheimer’s AssociationMary Kinross Charitable TrustHalpin TrustAge Related Diseases and Health TrustNorman Family Charitable TrustRosetrees TrustJames Tudor FoundationUK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul