The Cerebrospinal Fluid Free-Glycans Hex and HexNAcHexNeu5Ac as Potential Biomarkers of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting a growing number of elderly people. In order to improve the early and differential diagnosis of AD, better biomarkers are needed. Glycosylation is a protein post-translational modification that is modulated in the course of many diseases, including neurodegeneration.

Comparison of diagnostic routines for suspected Alzheimer's disease patients in US-American and German primary care.

Thorough diagnostics are a prerequisite for the optimal treatment of Alzheimer's disease (AD). Biomarker-based diagnostics are standard in academia, data on practitioners' diagnostic workups is scarce. Surveys in German and US healthcare providers (HCP) were conducted regarding diagnostics in presumed AD patients.

Influence of preanalytical and analytical factors on the quantification of six regulatory serum proteins.

We analyzed differences in protein concentrations in human blood serum depending on the tube material and the immunoassay platform used. Blood samples from study participants were collected in glass and polypropylene tubes (n = 292). Serum concentrations of six proteins (BDNF, IGF-1, VEGF-A, TGF-β1, MCP-1 and IL-18) were assessed by using ELISAs (all biomarkers), as well as a novel fully automated immunoassay platform (all but IGF-1, n = 211).

Long-term stability and age-dependence of six regulatory serum proteins.

The development of biomarker-based diagnostic procedures often relies on samples stored for several years. We aimed to investigate the influence of storage time and patient age on six neuroregulatory and immunoregulatory serum biomarkers. We quantified six biomarkers in serum from 151 individuals using ELISA.

Presenilin 1 Gene Mutation (M139V) in a German Family with Early-Onset Alzheimer's Disease: A Case Report.

Objective: This study describes a 44-year-old German male with early-onset Alzheimer's disease as a result of a M139V presenilin 1 mutation. The patient has at least seven affected family members, spanning at least four generations.

Method: We performed a complete demographic, genetic, neuropsychological, neuropsychiatric, neuroradiological, and neuropathological characterizations of this patient.

Diagnose it yourself: will there be a home test kit for Alzheimer's disease?

Alzheimer's disease is the most common neurodegenerative process leading to dementia. To date, there is no curative approach; thus, establishing a diagnosis as early as possible is necessary to implement preventive measures. However, today's gold standard for diagnosing Alzheimer's disease is high in both cost and effort and is not readily available.

Value of Neuropsychological Tests to Identify Patients with Depressive Symptoms on the Alzheimer's Disease Continuum.

Background: Depressive symptoms often co-occur with Alzheimer's disease (AD) and can impact neuropsychological test results. In early stages of AD, disentangling cognitive impairments due to depression from those due to neurodegeneration often poses a challenge.

Objective: We aimed to identify neuropsychological tests able to detect AD-typical pathology while taking into account varying degrees of depressive symptoms.

Value of a Panel of 6 Serum Biomarkers to Differentiate Between Healthy Controls and Mild Cognitive Impairment Due to Alzheimer Disease.

Background: There is considerable evidence suggesting that inflammatory responses may be involved in the neurodegenerative cascade of Alzheimer disease (AD). Blood-based biomarker analysis of inflammatory markers indicative of dementia could serve as a minimally invasive and easy-to-administer diagnostic tool in primary care.

Material And Methods: The authors quantified 6 markers (brain-derived neurotrophic factor, insulin-like growth factor 1, vascular endothelial growth factor, transforming growth factor-beta type 1, monocyte chemoattractant protein 1, and interleukin-18) in blood serum of 68 healthy blood donors (controls), 42 patients with AD at the dementia stage, 55 patients with AD at the stage of mild cognitive impairment (MCI-AD), and 25 patients with MCI non-AD.

Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling.

Introduction: Apolipoprotein E (apoE) is a carrier for brain lipids and the most important genetic risk factor for Alzheimer's disease (AD). ApoE binds the receptor sortilin, which mediates uptake of apoE-bound cargo into neurons. The significance of this uptake route for brain lipid homeostasis and AD risk seen with apoE4, but not apoE3, remains unresolved.

Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease.

Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems-wide changes of CSF protein levels that accompany AD.

Plasma Amyloid Concentration in Alzheimer's Disease: Performance of a High-Throughput Amyloid Assay in Distinguishing Alzheimer's Disease Cases from Controls.

Background: Collection of cerebrospinal fluid (CSF) for measurement of amyloid-β (Aβ) species is a gold standard in Alzheimer's disease (AD) diagnosis, but has risks. Thus, establishing a low-risk blood Aβ test with high AD sensitivity and specificity is of outmost interest.

Objective: We evaluated the ability of a commercially available plasma Aβ assay to distinguish AD patients from biomarker-healthy controls.

Definition and quantification of six immune- and neuroregulatory serum proteins in healthy and demented elderly.

Blood-based biomarkers related to immune- and neuroregulatory processes may be indicative of dementia but lack standardization and proof-of-principle studies. The blood serum collection protocol as well as the analytic procedure to quantify the markers BDNF, IGF-1, VEGF, TGF-β 1, MCP-1 and IL-18 in blood serum were standardized and their concentrations were compared between groups of 81 Alzheimer's disease patients and 79 healthy controls. Applying standardized methods, results for the quantification of the six markers in blood serum are stable and their concentrations significantly differ for all analytes except VEGF between patients diagnosed with Alzheimer's disease and healthy controls.

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer's Disease: A Pilot Study.

Background/aims: Major depressive disorder (MDD) can cooccur with early Alzheimer's disease (AD) or may cause memory problems independently of AD. Previous studies have suggested that the AD-related cerebrospinal fluid (CSF) biomarkers tau and Aβ(1-42) could help discriminate between early AD and depression unrelated to AD. Moreover, the postsynaptic protein neurogranin and presynaptic BACE1 have increasingly gained attention as potential new AD biomarkers, but they have not yet been investigated concerning depression.

Methods in endogenous steroid profiling - A comparison of gas chromatography mass spectrometry (GC-MS) with supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS).

In various fields of endocrinology, the determination of steroid hormones synthesised by the human body plays an important role. Research on central neurosteroids has been intensified within the last years, as they are discussed as biomarkers for various cognitive disorders. Their concentrations in cerebrospinal fluid (CSF) are considered to be regulated independently from peripheral fluids.

Tau plasma levels in subjective cognitive decline: Results from the DELCODE study.

Previous studies have demonstrated increased tau plasma levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD. Much less is known whether increased tau plasma levels can already be detected in the pre-MCI stage of subjective cognitive decline (SCD). In the present study we measured tau plasma levels in 111 SCD patients and 134 age- and gender-matched cognitively healthy controls participating in the DZNE (German Center for Neurodegenerative Diseases) longitudinal study on cognition and dementia (DELCODE).

Correlation of florbetaben PET imaging and the amyloid peptide Aß42 in cerebrospinal fluid.

Today, the use of biomarkers such as amyloid-specific positron emission tomography (PET) tracers and information derived from cerebrospinal fluid (CSF) can support the diagnosis of Alzheimer's disease (AD) as an indicator for the presence of amyloid pathology. We here show that the PET signal of the F-labelled tracer florbetaben (NeuraCeq™), that binds to amyloid-beta plaques, inversely correlates with CSF levels of Aß42, another biomarker for AD. Results from the two biomarkers were concordant in 35 out of 38 subjects.

Alzheimer amyloid peptide aβ42 regulates gene expression of transcription and growth factors.

The pathogenesis of Alzheimer's disease (AD) is characterized by the aggregation of amyloid-β (Aβ) peptides leading to deposition of senile plaques and a progressive decline of cognitive functions, which currently remains the main criterion for its diagnosis. Robust biomarkers for AD do not yet exist, although changes in the cerebrospinal fluid levels of tau and Aβ represent promising candidates in addition to brain imaging and genetic risk profiling. Although concentrations of soluble Aβ42 correlate with symptoms of AD, less is known about the biological activities of Aβ peptides which are generated from the amyloid-β protein precursor.

Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline.

The pathology of Alzheimer's disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-β (Aβ). Using the APPPS1 Alzheimer's disease mouse model, we found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of the IL-12/IL-23 signaling molecules p40, p35 or p19, in which deficiency of p40 or its receptor complex had the strongest effect, resulted in decreased cerebral amyloid load.

Long-term stability of Alzheimer's disease biomarker proteins in cerebrospinal fluid.

The quantitative analysis of peptides in human cerebrospinal fluid (CSF) has become an important step in the early diagnosis of dementia, e.g., Alzheimer's disease.

Antidepressants act on glial cells: SSRIs and serotonin elicit astrocyte calcium signaling in the mouse prefrontal cortex.

One important target in the treatment of major depressive disorder (MDD) is the serotonin (5-hydroxytryptamine, 5-HT) system. Selective serotonin reuptake inhibitors (SSRI) are used to treat MDD. Yet, the mode of action of these drugs is not completely understood.

Astrocyte function is modified by Alzheimer's disease-like pathology in aged mice.

Alzheimer's disease (AD) may affect all cell types in the central nervous system. Astrocytes have rarely been investigated in the aged brain and the role of astrocytes in AD is poorly understood. In this study, we used acute brain slices from an amyloid-beta overexpressing double transgenic mouse line where astrocytes express the enhanced green fluorescent protein under the control of the glial fibrillary acidic protein promoter.

Astrocytes discriminate and selectively respond to the activity of a subpopulation of neurons within the barrel cortex.

Sensory information from single whiskers in rodents projects to defined morphological units in the cortex, the barrels. We found that astrocytes selectively respond with an increase in the cytosolic Ca(2+) concentration to activation of layer 4 neurons, the input cells of the barrel columns. The neuronal Ca(2+) signal also spread across barrel column borders mainly in layer 2/3, but the glutamate-mediated astrocyte response stayed restricted to the barrel column.

Temperature and nitric oxide control spontaneous calcium transients in astrocytes.

Transient spontaneous increases in the intracellular Ca2+ concentration have been frequently observed in astrocytes in cell culture and in acutely isolated slices from several brain regions. Recent in vivo experiments, however, reported only a low frequency of spontaneous Ca2+ events in astrocytes. Since the ex vivo experiments were usually performed at temperatures lower than physiological body temperature, we addressed the question whether temperature could influence the spontaneous Ca2+ activity in astrocytes.

Multimodal gain control at the hippocampal Schaffer collateral-CA1 synapse.

Information processing at central nervous system synapses is shaped by long-lasting modifications, such as long-term potentiation and short-lived and putatively synapse-specific modifications by various forms of short-term plasticity, such as facilitation, potentiation, and depression. Using an extracellular paired-pulse facilitation (PPF) protocol at the Schaffer collateral-CA1 (SC) connection in acute hippocampal slices in mice, we extend previous reports of optimal signal gain at intermediate interpulse intervals obtained at single SC synapses to the network level. Moreover, maximum signal gain changed when the input intensity was altered.

Extracellular application of nicotinic acid adenine dinucleotide phosphate induces Ca2+ signaling in astrocytes in situ.

Nicotinic acid adenine dinucleotide phosphate (NAADP+) has been identified as a novel second messenger triggering Ca2+ release from intracellular stores. Here we report that murine cortical astrocytes in culture and in acute slices respond with transient intracellular Ca2+ increases to extracellularly applied NAADP+ and express the NAADP+-producing enzyme CD38. The Ca2+ transients triggered by NAADP+ occurred with an average delay of 35 s as compared with ATP-triggered Ca2+ signaling, suggesting that NAADP+ may have to enter the cell to act.