Safety and efficacy of plasma transfusion from exercise-trained donors in patients with early Alzheimer's disease: protocol for the ExPlas study.

Introduction: Given that exercise training reduces the risk of developing Alzheimer's disease (AD), induces changes in the blood composition and has widespread systemic benefits, it is reasonable to hypothesise that exercised plasma (ExPlas) may have rejuvenative properties. The main objective is to test safety and tolerability of transfusing ExPlas from young, healthy, fit adults to patients with mild cognitive impairment (MCI) or early AD. The study is a pilot for a future efficacy study.

Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden.

Importance: Identification of proteins and genetic factors that reduce Alzheimer disease (AD) pathology is of importance when searching for novel AD treatments. Heterozygosity of the KL-VS haplotype has been associated with reduced amyloid and tau burden. Whether this association is mediated by the Klotho protein remains unclear.

Cut-off evaluation of intrathecal oligoclonal bands of IgM in relapsing-remitting multiple sclerosis; a retrospective study.

Background: Multiple sclerosis (MS) is the most common demyelinating disease and characterized by immunological changes. Oligoclonal bands of IgG in CSF not seen in corresponding serum have been used for many years as part of the diagnostic criteria. However, considerably less is known about the role of IgM, despite several studies showing marked changes to IgM metabolism in MS.

Plasma apolipoprotein E levels in longitudinally followed patients with mild cognitive impairment and Alzheimer's disease.

Background: Low levels of plasma apolipoprotein E (apoE) and presence of the APOE ε4 allele are associated with an increased risk of Alzheimer's disease (AD). Although the increased risk of AD in APOE ε4-carriers is well-established, the protein levels have received limited attention.

Methods: We here report the total plasma apoE and apoE isoform levels at baseline from a longitudinally (24 months) followed cohort including controls (n = 39), patients with stable amnestic mild cognitive impairment during 24 months follow up (MCI-MCI, n = 30), patients with amnestic MCI (aMCI) that during follow-up were clinically diagnosed with AD with dementia (ADD) (MCI-ADD, n = 28), and patients with AD with dementia (ADD) at baseline (ADD, n = 28).

Time to Diagnosis in Young Onset Alzheimer's Disease: A Population-Based Study from Central Norway.

Background: Young onset dementia is associated with a longer time to diagnosis compared to late onset dementia. Earlier publications have indicated that atypical presentation is a key contributing factor to the diagnostic delay. Our hypothesis was that even the most common presentation of Alzheimer's disease is associated with a substantial diagnostic delay in patients < 65 years.

Incidence of Young Onset Dementia in Central Norway: A Population-Based Study.

Background: The epidemiology of young onset dementia is little researched compared to late onset dementia. Information on incidence rates is vital for medical professionals, and for government planning purposes.

Objective: To determine the incidence of young onset dementia in a defined catchment area of central Norway.

The Amyloid, Tau, and Neurodegeneration (A/T/N) Classification Applied to a Clinical Research Cohort with Long-Term Follow-Up.

Background: The unbiased amyloid, tau, and neurodegeneration (A/T/N) classification is designed to characterize individuals in the Alzheimer continuum and is currently little explored in clinical cohorts.

Objective: A retrospective comparison of the A/T/N classification system with the results of a two-year clinical study, with extended follow-up up to 10 years after inclusion.

Methods: Patients (n = 102) clinically diagnosed as Alzheimer's disease (AD) with dementia or amnestic mild cognitive impairment (MCI), and 61 cognitively healthy control individuals were included.

Author Correction: Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plasma Apolipoprotein E Monomer and Dimer Profile and Relevance to Alzheimer's Disease.

The APOEɛ4 gene variant is the strongest genetic risk factor for Alzheimer's disease (AD), whereas APOEɛ3 conventionally is considered as 'risk neutral' although APOEɛ3-carriers also develop AD. Previous studies have shown that the apolipoprotein E3 (apoE3) isoform occurs as monomers, homodimers and heterodimers with apolipoprotein A-II in human body fluids and brain tissue, but the relevance of a plasma apoE3 monomer/dimer profile to AD is unknown. Here we assessed the distribution of monomers, homodimers and heterodimers in plasma from control subjects and patients with mild cognitive impairment (MCI) and AD with either a homozygous APOEɛ3 (n = 31 control subjects, and n = 14 MCI versus n = 5 AD patients) or APOEɛ4 genotype (n = 1 control subject, n = 21 MCI and n = 7 AD patients).

The Prevalence and Subtypes of Young Onset Dementia in Central Norway: A Population-Based Study.

Background: Young onset dementia poses several challenges for the individual, health care, and society that are not normally relevant for late onset dementia, but is little researched.

Objective: To determine the prevalence and subtypes of young onset dementia in a defined catchment area in central Norway.

Methods: The main sources of patient identification were the databases at the Department of Neurology, University Hospital of Trondheim (St.

Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.

Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls).

Meta-analysis of Alzheimer's disease on 9,751 samples from Norway and IGAP study identifies four risk loci.

A large fraction of genetic risk factors for Alzheimer's Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer's Project (IGAP), denoted the discovery sample.

The relevance of cerebrospinal fluid α-synuclein levels to sporadic and familial Alzheimer's disease.

Accumulating evidence demonstrating higher cerebrospinal fluid (CSF) α-synuclein (αSyn) levels and αSyn pathology in the brains of Alzheimer's disease (AD) patients suggests that αSyn is involved in the pathophysiology of AD. To investigate whether αSyn could be related to specific aspects of the pathophysiology present in both sporadic and familial disease, we quantified CSF levels of αSyn and assessed links to various disease parameters in a longitudinally followed cohort (n = 136) including patients with sporadic mild cognitive impairment (MCI) and AD, and in a cross-sectional sample from the Dominantly Inherited Alzheimer's Network (n = 142) including participants carrying autosomal dominant AD (ADAD) gene mutations and their non-mutation carrying family members.Our results show that sporadic MCI patients that developed AD over a period of two years exhibited higher baseline αSyn levels (p = 0.

Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls.

Purpose: The reports regarding the status of the immune system in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have been inconclusive. We approached this question by comparing a strictly defined group of CFS/ME outpatients to healthy control individuals, and thereafter studied cytokines in subgroups with various psychiatric symptoms.

Materials And Methods: Twenty patients diagnosed with CFS/ME according to the Fukuda criteria and 20 age- and sex-matched healthy controls were enrolled in the study.

Assessment of kallikrein 6 as a cross-sectional and longitudinal biomarker for Alzheimer's disease.

Background: Kallikrein 6 (KLK6) is known to be an age-related protease expressed at high levels in the central nervous system. It was previously shown to be involved in proteolysis of extracellular proteins implicated in neurodegenerative diseases such as Alzheimer's disease (AD), prompting validation of KLK6 as a potential biomarker of disease. However, analyses of both plasma and cerebrospinal fluid (CSF) levels of KLK6 in patients with AD have been inconclusive.

Cerebrospinal Fluid Aβ43 Is Reduced in Early-Onset Compared to Late-Onset Alzheimer's Disease, But Has Similar Diagnostic Accuracy to Aβ42.

Unlabelled: Amyloid beta 1-43 (Aβ43) may be a useful additional biomarker for diagnosing Alzheimer's disease (AD). We have investigated cerebrospinal fluid (CSF) levels of Aβ43 in patients with early-onset AD in contrast to levels in late-onset AD. For comparison, in addition to the 'core' biomarkers, several other analytes were also determined [YKL-40, neurofilament light (NF-L), glial fibrillary acidic protein (GFAP), and progranulin].

A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging.

Introduction: Changes in cerebrospinal fluid (CSF) tau and amyloid β (Aβ)42 accompany development of Alzheimer's brain pathology. Robust tau and Aβ42 immunoassays were developed to establish a tau/Aβ42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects.

Methods: A CSF tau/Aβ42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET.

Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer's Disease.

Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer's disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer's disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer's disease has never been assessed.

Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer's disease, mild cognitive impairment, or healthy controls: a two year follow-up study.

Background: α-Synuclein has been proposed as a potential biomarker for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, results from α-synuclein measurements in cerebrospinal fluid (CSF) have been inconclusive, and to our knowledge, longitudinal studies of changes prior to the AD diagnosis have not been investigated.

Methods: Levels of α-synuclein at baseline and after one and two years were measured in CSF, by enzyme-linked immunosorbent assay.

Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study.

Introduction: Biomarkers that will reliably predict the onset of Alzheimer's disease (AD) are urgently needed. Although cerebrospinal fluid (CSF) amyloid beta 1-42 (Aβ42), total tau, and phosphorylated tau can be used to complement the clinical diagnosis of AD, amnestic mild cognitive impairment (aMCI), the prodromal phase of AD, is heterogeneous. Biomarkers should be able to determine which patients with aMCI are at greatest risk of AD.

Association of Butyrylcholinesterase-K Allele and Apolipoprotein E ɛ4 Allele with Cognitive Decline in Dementia with Lewy Bodies and Alzheimer's Disease.

Background: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias.

Objective: To determine the association of BCHE-K and APOEɛ4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients.

Effect of Tween-20 on Core Biomarkers Measured in Cerebrospinal Fluid from Patients with Alzheimer's Disease, Mild Cognitive Impairment, or Healthy Control Individuals.

Background: There is substantial variation caused by preanalytical procedures in the measurement of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) reported in the literature.

Objective: Determine whether the detergent Tween-20 improves diagnostic accuracy.

Methods: CSF proteins (Aβ42, Aβ40, total tau, and phosphorylated tau) were measured by standard ELISA, in uncentrifuged CSF with or without 0.

Changes to Intermediary Metabolites in Sporadic and LRRK2 Parkinson's Disease Demonstrated by Proton Magnetic Resonance Spectroscopy.

Background. Parkinson's disease (PD) remains a clinical diagnosis and biomarkers are needed to detect the disease as early as possible. Genetically determined PD provides an opportunity for studying metabolic differences in connection with disease development.

Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease.

Background: Epidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis.

Methods And Results: Using summary statistics (P values and odds ratios) from genome-wide association studies of >200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels.

Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease.

We conducted a search for rare, functional variants altering susceptibility to Alzheimer's disease that exploited knowledge of common variants associated with the same disease. We found that loss-of-function variants in ABCA7 confer risk of Alzheimer's disease in Icelanders (odds ratio (OR) = 2.12, P = 2.