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  1. Article ; Online: Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome

    Claudia Cannavo / Karen Cleverley / Cheryl Maduro / Paige Mumford / Dale Moulding / Elizabeth M. C. Fisher / Frances K. Wiseman

    PLoS ONE, Vol 17, Iss

    2022  Volume 5

    Abstract: Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor ... ...

    Abstract Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes, and changes to endosome biology occur early in Alzheimer’s disease. Here, we determine if primary mouse embryonic fibroblasts isolated from a mouse model of Down syndrome can be used to study endosome and APP cell biology. We report that in this cellular model, endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in the model, despite three copies of App.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome.

    Claudia Cannavo / Karen Cleverley / Cheryl Maduro / Paige Mumford / Dale Moulding / Elizabeth M C Fisher / Frances K Wiseman

    PLoS ONE, Vol 17, Iss 5, p e

    2022  Volume 0262558

    Abstract: Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer's disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor ... ...

    Abstract Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer's disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes, and changes to endosome biology occur early in Alzheimer's disease. Here, we determine if primary mouse embryonic fibroblasts isolated from a mouse model of Down syndrome can be used to study endosome and APP cell biology. We report that in this cellular model, endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in the model, despite three copies of App.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Specific cortical and subcortical grey matter regions are associated with insomnia severity.

    Neus Falgàs / Ignacio Illán-Gala / Isabel E Allen / Paige Mumford / Youssef M Essanaa / Michael M Le / Michelle You / Lea T Grinberg / Howard J Rosen / Thomas C Neylan / Joel H Kramer / Christine M Walsh

    PLoS ONE, Vol 16, Iss 5, p e

    2021  Volume 0252076

    Abstract: Background There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, ... ...

    Abstract Background There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen. Methods 120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed. Results ISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  4. Article ; Online: Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models

    Justin L. Tosh / Elena R. Rhymes / Paige Mumford / Heather T. Whittaker / Laura J. Pulford / Sue J. Noy / Karen Cleverley / LonDownS Consortium / Matthew C. Walker / Victor L. J. Tybulewicz / Rob C. Wykes / Elizabeth M. C. Fisher / Frances K. Wiseman

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid ... ...

    Abstract Abstract Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  5. Article ; Online: Publisher Correction

    Justin L. Tosh / Elena R. Rhymes / Paige Mumford / Heather T. Whittaker / Laura J. Pulford / Sue J. Noy / Karen Cleverley / LonDownS Consortium / Matthew C. Walker / Victor L. J. Tybulewicz / Rob C. Wykes / Elizabeth M. C. Fisher / Frances K. Wiseman

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    Genetic dissection of down syndrome‑associated alterations in APP/amyloid‑β biology using mouse models

    2021  Volume 2

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  6. Article ; Online: REM sleep is associated with white matter integrity in cognitively healthy, older adults.

    Marie Altendahl / Devyn L Cotter / Adam M Staffaroni / Amy Wolf / Paige Mumford / Yann Cobigo / Kaitlin Casaletto / Fanny Elahi / Leslie Ruoff / Samirah Javed / Brianne M Bettcher / Emily Fox / Michelle You / Rowan Saloner / Thomas C Neylan / Joel H Kramer / Christine M Walsh

    PLoS ONE, Vol 15, Iss 7, p e

    2020  Volume 0235395

    Abstract: There is increasing awareness that self-reported sleep abnormalities are negatively associated with brain structure and function in older adults. Less is known, however, about how objectively measured sleep associates with brain structure. We objectively ...

    Abstract There is increasing awareness that self-reported sleep abnormalities are negatively associated with brain structure and function in older adults. Less is known, however, about how objectively measured sleep associates with brain structure. We objectively measured at-home sleep to investigate how sleep architecture and sleep quality related to white matter microstructure in older adults. 43 cognitively normal, older adults underwent diffusion tensor imaging (DTI) and a sleep assessment within a six-month period. Participants completed the PSQI, a subjective measure of sleep quality, and used an at-home sleep recorder (Zeo, Inc.) to measure total sleep time (TST), sleep efficiency (SE), and percent time in light sleep (LS), deep sleep (DS), and REM sleep (RS). Multiple regressions predicted fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum as a function of total PSQI score, TST, SE, and percent of time spent in each sleep stage, controlling for age and sex. Greater percent time spent in RS was significantly associated with higher FA (β = 0.41, p = 0.007) and lower MD (β = -0.30, p = 0.03). Total PSQI score, TST, SE, and time spent in LS or DS were not significantly associated with FA or MD (p>0.13). Percent time spent in REM sleep, but not quantity of light and deep sleep or subjective/objective measures of sleep quality, positively predicted white matter microstructure integrity. Our results highlight an important link between REM sleep and brain health that has the potential to improve sleep interventions in the elderly.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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