Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells.

Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production.

Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells.

Background: Alzheimer's disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18) in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein.

Neuropsychiatric symptoms and quality of life in patients with very mild and mild Alzheimer's disease.

Background: Neuropsychiatric symptoms (NPS) are common manifestations of Alzheimer' s disease (AD).

Objective: To examine the prevalence and significance of NPS in very mild and mild AD patients with emphasis on their influence on the well-being of the patients and their caregivers.

Methods: The participants were 240 patient-caregiver dyads who participated in a prospective, controlled rehabilitation study (ALSOVA).

[Update on current care guidelines. The diagnosis and medical treatment of memory disorders].

Any complaints from a patient about their memory should be examined. Diagnosis is based on international criteria. The basic evaluation consists of the medical history, clinical evaluation, cognitive tests and brain imaging, especially using MRI.

[Early detection of cognitive changes in memory diseases: new cut-off scores for the Finnish version of CERAD neuropsychological battery].

The evaluation of cognitive functions by using CERAD (Consortium to Establish a Registry for Alzheimer's Disease) is recommended as a tool in basic health care for screening of memory diseases. The reliability of this method, adopted in Finland in 1999, has been impaired by the fact that there have been no comprehensive Finnish norms to serve as the basis for the cut-off limits of the test tasks. This article presents the new, revised cut-off values for the CERAD procedure, based on the comparison of Finnish population-based normative data with those of persons having very mild or mild Alzheimer's disease.

Amyloid and tau proteins in cortical brain biopsy and Alzheimer's disease.

Objective: Amyloid-β(Aβ) aggregates are presumed to be found in the brain at an early stage of Alzheimer's disease (AD) but have seldom been assessed by brain biopsy during life in often elderly patients.

Methods: Between 1991 and 2006 we evaluated 468 patients with suspected normal pressure hydrocephalus with intraventricular pressure monitoring and a right frontal cortical biopsy sample immunostained for Aβ and hyperphosphorylated tau (HPτ). Adequate samples and the clinical follow-up data until death or the end of 2008, available in 433 cases, were reviewed for the clinical signs of dementia, including AD.

[Update on current care guidelines: diagnostics, treatment and rehabilitation of multiple sclerosis].

Treatment is initiated when the McDonald criteria for relapsing-remitting multiple sclerosis (RRMS) are fulfilled. High-risk patients with clinically isolated syndrome are followed using magnetic resonance imaging for one year after the first imaging. Interferon-beta or glatiramer acetate are the first-line immunomodulating drugs (IMD) for RRMS.

Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene.

Genetic risk for multiple sclerosis (MS) is thought to involve both common and rare risk alleles. Recent GWAS and subsequent meta-analysis have established the critical role of the HLA locus and identified new common variants associated to MS. These variants have small odds ratios (ORs) and explain only a fraction of the genetic risk.

An update on clinical proteomics in Alzheimer's research.

Alzheimer's disease (AD) is a pathologically complex and aetiologically multifactorial dementing disorder affecting millions of people worldwide. The pathological brain changes are assumed to occur decades prior to the onset of clinical symptoms. The diagnosis of early AD remains problematic and is mainly based on clinical and neuropsychological findings after the onset of symptoms.

CALHM1 P86L polymorphism does not alter amyloid-beta or tau in cerebrospinal fluid.

Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimer's disease (AD). Moreover, the risk allele increased amyloid-beta (A beta) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate A beta or tau levels in cerebrospinal fluid (CSF).

[Use of CSF biomarkers in the diagnostics of memory diseases].

Alzheimer's disease is the most common cause of dementia. Early diagnosis of diseases leading to dementia is cost-effective. However, early diagnosis of Alzheimer's disease may be difficult and should not be based on exclusion of other reasons for dementia.

Caregiver depression is associated with a low sense of coherence and health-related quality of life.

Objectives: The main objective is to examine the sense of coherence (SOC) of spouse caregivers. The aim was further investigate the association of SOC, health-related quality of life (HRQoL), depressive symptoms, distress and how severity of Alzheimer's disease (AD) affects SOC.

Method: 17O patient-spouse caregiver dyads in which the patient has recently diagnosed mild AD.

Neurofilament ELISA validation.

Background: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.

Methods: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples.

CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.

Context: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted.

Objective: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI.

Design, Setting, And Participants: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007.

Tenomodulin variants, APOE and Alzheimer's disease in a Finnish case-control cohort.

The tenomodulin gene (TNMD, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between TNMD and phenotypes, which are related to increased risk of AD. The common sequence variation in the TNMD was not associated with prevalence of AD among 526 cases and 672 controls.

Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study.

Background: Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is characterised by decreased CSF concentrations of Abeta(42) and increased concentrations of tau. We investigated the prevalence of a CSF AD profile in patients with SCI, naMCI, or aMCI and the association of this profile with cognitive outcome in each group.

Cerebrospinal fluid tau as a marker of neuronal damage after epileptic seizure.

Purpose: Whether repeated brief seizures can cause neuronal damage is controversial. Cerebrospinal fluid (CSF) total tau (T-tau) and phosphorylated tau (P-tau) measurements have been suggested for the diagnosis of Alzheimer's disease, and T-tau may also be a marker of axonal damage and neuronal degeneration. We studied T-tau and P-tau levels and P-tau/T-tau ratio in CSF after epileptic seizures in order to determine whether they are increased after seizures.

Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain.

Background: There is a clear need to develop an objective diagnostic test for Alzheimer disease (AD). Changes in the levels of cerebrospinal fluid (CSF) tau protein and beta-amyloid 42 (Abeta42) peptide in patients with AD have been well documented, but the relationship between these biomarkers and neuropathologic changes in the brain is not established.

Objective: To study the relationship between antemortem CSF biomarker levels and Alzheimer-type neuropathologic changes in the brain.

Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS.

Large case-control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare, possibly more penetrant alleles. One strategy is to use special populations with a founder effect and isolation, resulting in allelic enrichment.

A follow-up study of chromosome 19q13 in multiple sclerosis susceptibility.

A possible role of allelic variation on chromosome 19q13 in multiple sclerosis (MS) susceptibility has been suggested. We tested association of sixteen 19q13 markers with MS in 459 families. Nominally significant associations were tested in an independent set of 323 families as well as in the pooled set of 782 families.

MYO9B polymorphisms in multiple sclerosis.

Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed.

No evidence for shared etiology in two demyelinative disorders, MS and PLOSL.

Loss-of-function mutations of DAP12 and TREM2 cause a recessively inherited disease PLOSL, manifesting in brain white matter. The genes of the DAP12-TREM2 signaling receptor are located on 19q13.12 and 6p21.

Treatment with galantamine and time to nursing home placement in Alzheimer's disease patients with and without cerebrovascular disease.

Objective: This study evaluated patient and treatment (galantamine and other acetylcholinesterase inhibitors (AChEIs)) factors associated with the time until nursing home placement (NHP) in patients with Alzheimer's disease (AD) with and without cerebrovascular disease (CVD).

Methods: Re-contact follow-up study conducted in 2004 of 548 patients who had previously participated in RCTs with galantamine. Time to NHP was analyzed using Kaplan-Meier estimates and Cox regression analysed factors associated with NHP.

Interleukin-18 increases expression of kinases involved in tau phosphorylation in SH-SY5Y neuroblastoma cells.

Inflammatory cytokines, produced mainly by activated microglia in the brain, can enhance neuronal degeneration and the amyloid-beta-plaque production involved in Alzheimer's disease (AD). We previously demonstrated that the expression of the pro-inflammatory cytokine interleukin-18 (IL-18) colocalizes with plaques and hyperphoshorylated tau containing neurons in AD patients. Here we exposed neuron-like, differentiated SH-SY5Y neuroblastomas to IL-18 and observed that the protein levels of p35, Cdk5, GSK-3beta, and Ser15-phosphorylated p53 increased during 6 h-24 h.