The Ts65Dn mouse is the best-studied animal model for Down syndrome. In the experiments described here, NMDA-mediated or mGluR-mediated LTD was induced in the CA1 region of hippocampal slices from Ts65Dn and euploid control mice by bath application of 20 µM NMDA for 3 min and 50 µM DHPG for 5 min, respectively. We found that Ts65Dn mice display exaggerated NMDA-induced, but not mGluR-induced, LTD in the CA1 region of the hippocampus compared with euploid control animals. In addition, this abnormal level of LTD can be pharmacologically rescued by the NMDA receptor antagonist memantine.
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http://dx.doi.org/10.1101/lm.024182.111 | DOI Listing |
Alzheimers Dement
December 2024
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Background: Increased APP gene dosage is both necessary and sufficient to result in Down Syndrome Alzheimer's Disease (DSAD) in humans and AD-related degenerative changes in mouse models of DS.
Method: We tested antisense oligonucleotides (ASOs) designed to suppress APP expression via RNAseH1-mediated degradation in the Dp(16)1Yey or Dp(16) model of Down Syndrome. Dp(16) is trisomic for human chromosome 21 syntenic regions on murine chromosome 16, containing 115 genes including APP.
Background: Clinical assessments utilized in trials to measure progression in sporadic Alzheimer's disease (SAD) such as the MMSE, ADAS-Cog, CDR-SB and ADCS-ADL are well established. Distinct assessments are utilized for Down Syndrome-related Alzheimer's disease (DSAD). Although these assessments are less well established, they probe comparable domains of cognition and function.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Siemens Heathineers, Princeton, NJ, USA.
Background: The recent breakthrough in monoclonal antibody treatment for Alzheimer's disease (AD) has ushered in a new phase in AD healthcare. However, associated amyloid-related imaging abnormalities (ARIA) present a significant risk to patients, necessitating careful monitoring. Detection by radiologists can be challenging and may suffer from inconsistency.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Psychology & Language Sciences, University College London, London, United Kingdom.
Background: Dysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA), but remains poorly characterised in these syndromes. We hypothesised that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features and associated with atrophy affecting regions implicated in swallowing control.
Methods: In a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant (sv)PPA, 13 logopenic variant (lv)PPA).
Alzheimers Dement
December 2024
Hospital Alemão Oswaldo Cruz, São Paulo, São Paulo, Brazil.
Background: People with dementia (PWD) have several unmet needs during the syndrome progression. More unmet needs are related to worse outcomes, such as hospitalizations, injuries, and death. The caregiving burden has been related to more PWD unmet needs.
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