ABSTRACT
BACKGROUND: Adults with Down syndrome (DS) are at increased risk of developing Alzheimer's disease (AD) due to genetic predisposition. Identification of patients with AD is difficult since intellectual disabilities (ID) may confound diagnosis. The objective of this study was to evaluate the ability of the French version of the modified cued recall test (mCRT) to distinguish between subjects with and without AD in the adult DS population. METHODS: This was a retrospective, single-centre, medical records study including data between March 2014 and July 2020. Adults aged ≥30 years with DS who had at least one mCRT record available were eligible. Age, sex and ID level were extracted, and subjects were attributed to three groups: patients with AD, patients with co-occurring conditions that may impact cognitive function and subjects without AD. mCRT scores, adjusted by sex, age and ID level, were compared between groups. The optimal cut-off value to distinguish between patients with and without AD was determined using the receiver operating characteristic curve. The impact of age and ID level on mCRT scores was assessed. RESULTS: Overall, 194 patients with DS were included: 12 patients with AD, 94 patients with co-occurring conditions and 88 healthy subjects. Total recall scores were significantly lower (P < 0.0001) in patients with AD compared with healthy subjects. The optimal cut-off value to discriminate between patients with AD and healthy subjects was 22, which compares well with the cut-off value of 23 originally reported for the English version of the mCRT. Patients aged 30-44 years had higher mCRT total recall scores compared with patients aged ≥45 years (P = 0.0221). Similarly, patients with mild ID had higher mCRT scores compared with patients with severe ID (P < 0.0001). INTERPRETATION: The mCRT is a sensitive tool that may help in the clinical diagnosis of AD in subjects with DS. Early recognition of AD is paramount to deliver appropriate interventions to this vulnerable population.
Subject(s)
Alzheimer Disease , Down Syndrome , Intellectual Disability , Adult , Alzheimer Disease/diagnosis , Down Syndrome/diagnosis , Down Syndrome/psychology , Humans , Intellectual Disability/diagnosis , Intellectual Disability/epidemiology , Medical Records , Mental Recall , Neuropsychological Tests , Retrospective StudiesABSTRACT
Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1. As to the mechanism, expression of VP16-CREB, a constitutively active CREB mutant, had no effect on basal cytosolic calcium levels, extracellular calcium entry, or calcium mobilization from lysosomal-related acidic stores. Rather, VP16-CREB upregulated sigma-1 receptor expression thereby increasing the release of calcium from the endoplasmic reticulum and its uptake by mitochondria. Sigma-1 receptor was also upregulated in vivo upon VP16-CREB expression in astrocytes. We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum-mitochondria interface, which might be an astrocyte-based form of long-term depression.
Subject(s)
Astrocytes/metabolism , Calcium Signaling , Calcium/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Receptors, sigma/metabolism , Aging/metabolism , Animals , Cytosol/metabolism , Mice, Transgenic , Mitochondria/metabolism , Neurotransmitter Agents/metabolism , Rats, Sprague-Dawley , Subcellular Fractions/metabolism , Transcription, Genetic , Up-Regulation , Sigma-1 ReceptorABSTRACT
No disponible
Subject(s)
Adult , Female , Humans , Thyroid Crisis , Carcinoma, Adenosquamous , Postoperative Complications , Preoperative Care , Anesthesia , Hyperthyroidism , Uterine Cervical NeoplasmsABSTRACT
The behaviour of different batches of synthetic Poly(A).Poly(U) in reversed-phase high-performance liquid chromatography (HPLC) was studied. They consist of large molecules mainly in the form of a double strand. Differences in the elution patterns were correlated with properties detected by conventional methods such as electrophoresis, centrifugation, fusion analysis or enzymatic digestions. Under the present conditions, contamination by products and precursors used during synthesis was detectable, but was absent in most of the preparations. The differences in elution patterns between batches appear to be correlated with the size of the molecules synthesized. The chromatograms suggested that Poly(A).Poly(U) molecules contain single-strand portions at least transiently. The presence of such portions was confirmed by enzymatic digestion with S1 nuclease. The rapidity, reproducibility and ease of reversed-phase HPLC qualify this technique as a tool for routine analysis.
