Journal of Alzheimer's disease : JAD
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Cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for the diagnosis of Alzheimer's disease (AD). Since interpretation of CSF profile requires the combination of three parameters, biological data are not always conclusive and isolated elevation of phosphorylated tau (P-tau) or reduction of amyloid-β (Aβ)42 alone can be observed. In these cases, Aβ42/Aβ40 ratio could be more relevant than Aβ42 absolute values by considering inter-individual variations in the total amyloid load. ⋯ Our results support the use of the Aβ42/Aβ40 ratio in addition to the usual CSF AD biomarkers for patients with ambiguous biological profiles. This method could be specifically directed to this population in order to improve the level of certainty for clinical routine practice.
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The involvement of retina and its vasculature has been recently described in Alzheimer's disease (AD). However, none of the previous works have yet investigated the choroid in vivo. ⋯ Compared with healthy subjects, patients with AD showed a significant reduction in choroidal thickness. Choroidal thinning may represent an adjunctive biomarker for the diagnosis and follow-up of this disease.
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Cerebral hypometabolism of glucose, weight loss, and decreased food intake are characteristic features of sporadic Alzheimer's disease (AD). A systematic study on the serum levels of adipokines and insulin, the major hormones regulating energy metabolism, food intake, and body weight, in sporadic AD is necessary. The present study compares the serum levels of leptin, adiponectin, and insulin, measured by commercially available immuno-assay kits, between controls and sporadic AD subjects. ⋯ The changes in the serum levels of adiponectin and insulin in AD are positively correlated with the severity of dementia. Likewise, the serum level of leptin in AD subjects is negatively correlated with the degree of dementia. The changes in the levels of adipokines and insulin have implications in the amyloid pathology, neurodegeneration, and hypometabolism of glucose existing in the AD brain.
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There is a need to seek new treatment(s) for Alzheimer's disease (AD). A recent study showed that AD patients may have decreased levels of functional GABA receptors. Propofol, a commonly used anesthetic, is a GABA receptor agonist. ⋯ Here we showed that the propofol treatment improved cognitive function and attenuated brain caspase-3 and caspase-9 activation in both aged WT and AD Tg mice. Propofol attenuated Aβ-induced caspase-3 activation and opening of the mitochondrial permeability transition pore in the cells, and flumazenil inhibited the propofol's effects. These results suggested that propofol might improve cognitive function via attenuating the Aβ-induced mitochondria dysfunction and caspase activation, which explored the potential that anesthetic propofol could improve cognitive function in elderly and AD patients.
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Scales of global cognition and behavior, often used as endpoints for intervention trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI), are insufficiently responsive (i.e., relatively insensitive to change). Large patient samples are needed to detect beneficial drug effects. Therefore, magnetic resonance imaging (MRI) measures of cerebral atrophy have been proposed as surrogate endpoints. ⋯ Neuropsychological assessment is more responsive than MRI measures of brain atrophy for detecting disease progression in memory clinic patients with MCI or AD.