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Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer’s disease: a cohort study

on cognitive outcomes involving non-tau-related mechanisms. KeywordsAPOE Tau Atrophy Cognition Alzheimer’s disease  Niklas Mattsson and Rik Ossenkoppele contributed equally to this work. Electronic

Effects of surgery and propofol-remifentanil total intravenous anesthesia on cerebrospinal fluid biomarkers of inflammation, Alzheimer’s disease, and neuronal injury in humans: a cohort study

Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer’s disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid β production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal...

A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer’s disease

We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer’s disease (AD) patients, 40 subjects...

Preclinical effects of APOE ε4 on cerebrospinal fluid Aβ42 concentrations

Background From earlier studies it is known that the APOE ε2/ε3/ε4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1–42 (Aβ42) in patients with cognitive decline due to Alzheimer’s disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the...

Cerebrospinal fluid biomarkers for Alzheimer disease and subcortical axonal damage in 5,542 clinical samples

Introduction The neuronal loss in Alzheimer disease (AD) has been described to affect grey matter in the cerebral cortex. However, in the elderly, AD pathology is likely to occur together with subcortical axonal degeneration on the basis of cerebrovascular disease. Therefore, we hypothesized that biomarkers for AD and subcortical axonal degeneration would correlate in patients...

Lessons from Multicenter Studies on CSF Biomarkers for Alzheimer's Disease

Academic Editor: Lucilla Parnetti Copyright © 2010 Niklas Mattsson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use

Peptidome Analysis of Cerebrospinal Fluid by LC-MALDI MS

We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000–4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been...

To Know or Not to Know: Ethical Issues Related to Early Diagnosis of Alzheimer's Disease

Institutet, 171 77 Stockholm, Sweden Received 19 April 2010; Accepted 7 May 2010 Academic Editor: Lucilla Parnetti Copyright © 2010 Niklas Mattsson et al. This is an open access article distributed under ... GlaxoSmithKline. The other authors have no conflicts of interest. Author Contributions Niklas Mattsson and David Brax had the idea for this work and drafted the paper. Henrik Zetterberg made important revisions

To Know or Not to Know: Ethical Issues Related to Early Diagnosis of Alzheimer's Disease

Institutet, 171 77 Stockholm, Sweden Received 19 April 2010; Accepted 7 May 2010 Academic Editor: Lucilla Parnetti Copyright © 2010 Niklas Mattsson et al. This is an open access article distributed

Cerebrospinal Fluid Analysis Should Be Considered in Patients with Cognitive Problems

Hepatologists assay liver enzymes and cardiologists structural heart proteins in serum to diagnose and monitor their patients. This way of thinking has not quite made it into the memory clinics yet, in spite of the availability of validated cerebrospinal fluid biomarkers for key pathological events in the brain in neurodegeneration. Here, we argue that a spinal tap should be...

β-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage

Introduction The β-secretase enzyme, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), cleaves amyloid precursor protein (APP) in the first step in β-amyloid (Aβ) peptide production. Thus, BACE1 is a key target for candidate disease-modifying treatment of Alzheimer’s disease. In a previous exploratory Aβ biomarker study, we found that BACE1 inhibitor treatment resulted...

Use of theragnostic markers to select drugs for phase II/III trials for Alzheimer disease

In a slowly progressive disorder like Alzheimer disease, evaluation of the clinical effect of novel drug candidates requires large numbers of patients and extended treatment periods. Current cell- and animal-based disease models of Alzheimer disease are poor at predicting a positive treatment response in patients. To help bridge the gap between disease models and large and costly...

Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimer’s Disease

The success of future intervention strategies for Alzheimer’s disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable...

Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection

Background It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not...

Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders, Mild Cognitive Impairment and Alzheimer’s Disease

BackgroundCerebrospinal fluid (CSF) α-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF α-synuclein in Alzheimer’s disease (AD). No study has explored effects of CSF α-synuclein on brain atrophy. Here we tested if baseline CSF α-synuclein affects brain atrophy rates and if these effects vary across brain...

Cerebrospinal Fluid (CSF) 25-Hydroxyvitamin D Concentration and CSF Acetylcholinesterase Activity Are Reduced in Patients with Alzheimer's Disease

BackgroundLittle is known of vitamin D concentration in cerebrospinal fluid (CSF) in Alzheimer´s disease (AD) and its relation with CSF acetylcholinesterase (AChE) activity, a marker of cholinergic function. MethodsA cross-sectional study of 52 consecutive patients under primary evaluation of cognitive impairment and 17 healthy controls. The patients had AD dementia or mild...

Biomarkers for Microglial Activation in Alzheimer's Disease

Intensive research over the last decades has provided increasing evidence for neuroinflammation as an integral part in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Inflammatory responses in the central nervous system (CNS) are initiated by activated microglia, representing the first line of the innate immune defence of the brain. Therefore...

Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism

Background The metabolism of amyloid precursor protein (APP) and β-amyloid (Aβ) is widely studied in Alzheimer's disease, where Aβ deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other...

BACE1 Inhibition Induces a Specific Cerebrospinal Fluid β-Amyloid Pattern That Identifies Drug Effects in the Central Nervous System

BACE1 is a key enzyme for amyloid-β (Aβ) production, and an attractive therapeutic target in Alzheimer's disease (AD). Here we report that BACE1 inhibitors have distinct effects on neuronal Aβ metabolism, inducing a unique pattern of secreted Aβ peptides, analyzed in cell media from amyloid precursor protein (APP) transfected cells and in cerebrospinal fluid (CSF) from dogs by...