Current Alzheimer Research - Volume 13, Issue 6, 2016

Mitochondrial perturbations such as oxidative stress, increased fission/fusion dysfunction, and mitophagy are consistent features of Alzheimer’s disease (AD), yet the mechanisms that initiate these perturbations are unclear. One potential source for mitochondrial defects could be an imbalance in mitochondrial proteostasis. In this regard, studies indicate that a specialized mitochondrial unfolded protein response (mtU Read More

Most data indicates that Alzheimer’s disease involves an accumulation of amyloid β - peptide (Aβ) in the CNS and that sporadic cases arise from a deficiency in Aβ clearance. Considerable attention has been given to mechanisms by which Aβ might be transported between the brain and blood, and evidence suggests that p-glycoprotein, also known as the multi-drug resistance (MDR) protein (product of the ABCB1 gene), plays a Read More

Accumulation of intraneuronal amyloid-β peptide (Aβ) appears to be an early event in Alzheimer's disease (AD), suggesting its important role in the neurodegenerative process of AD. It is indicated that intracellular Aβ originates from a portion of Aβ, which is not secreted and consequently remains intracellular, or alternatively from the secreted Aβ, which is internalized into intracellular Aβ pool. A number of cell and transge Read More

In the present study we set up a model of slow progression of neuronal injury by exposing organotypic hippocampal cultures to a low concentration of Amyloid β (25-35) peptide (Aβ, 2 μM) to analyze the time-related effects of 17-β estradiol (17β-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition of 17β-E2 24 h prior to, together with or 48 h after exposure to Aβ. This effect is mimicked by selective ERα agoni Read More

Numerous efforts have been made in the last years to discover potential biomarkers of Alzheimer’s disease and its progression from mild cognitive impairment, considered as an intermediate phase in the development of Alzheimer’s disease from normal aging. However, there is still a considerable lack of understanding about pathological mechanisms underlying to disease. In the present study, serum metabolomics ba Read More

Altered progranulin levels play a major role in neurodegenerative diseases, like Alzheimer’s dementia (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), even in the absence of GRN mutations. Increasing progranulin levels could hereby provide a novel treatment strategy. However, knowledge on progranulin regulation in neurodegenerative diseases remains limited. We here demonstrate that cere Read More

Reducing amyloid-β (Aβ) accumulation is a promising strategy for developing Alzheimer’s Disease (AD) therapeutics. We recently reported that a triphenylmethane food dye analog, Brilliant Blue G (BBG), is a dose-dependent modulator of in vitro amyloid-β aggregation and cytotoxicity in cell-based assays. Following up on this recent work, we sought to further evaluate this novel modulator in a therapeutically-relevant AD tran Read More

Naming impairment in Alzheimer’s disease dementia (AD) is associated with atrophy of the left anterior temporal lobe (ATL). We aimed to elucidate if regional cerebral glucose metabolism, as a biomarker of synaptic dysfunction and neurodegeneration, of the left ATL predicts naming impairment, and if amyloid-beta (Aβ) deposition, a pathological hallmark of AD, contributes to the prediction. Twenty-nine patients with Read More

Recommended guidelines for the diagnosis of dementia due to Alzheimer’s Disease (AD) were revised in recent years, including Positron Emission Tomography (PET) as an in-vivo diagnostic imaging technique for the diagnosis of neurodegeneration. In particular PET, using 18Ffluorodeoxiglucouse ([18F]FDG), is able to detect very early changes of glucose consumption at the synaptic level, enabling to suppo Read More

Positron emission tomography (PET) provides a functional imaging modality to detect signs of dementias in human brains. Two-dimensional empirical mode decomposition (2D-EMD) provides means to analyze such images. It decomposes the latter into characteristic modes which represent textures on different spatial scales. These textures provide informative features for subsequent classification purposes. The st Read More

Background: Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 as the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer’s disease (AD). However, it is unclear the APOE-rs405509 interaction effect on brain spontaneous activity. Methods: We analyzed the interaction of the rs405509 TT allele and the APOE 4 allele on cognitive performances measured using neuropsychological Read More

Background: To date, very little is known about the nature of sarcopenia in subjects with cognitive impairment. The aims of this study were firstly to clarify the prevalence of sarcopenia at various stages of cognitive impairment, and secondly to examine factors related to sarcopenia in men and women with cognitive impairment. Method: The subjects were 418 outpatients (normal cognition; NC: 35, amnestic mild cognitive impair Read More