CSF ApoE predicts clinical progression in nondemented APOEε4 carriers.

Possible associations between cerebrospinal fluid (CSF) and plasma apolipoprotein E (ApoE) concentration and early clinical and pathophysiological manifestation of Alzheimer's disease were studied in a large and well-defined population of nondemented patients. CSF and plasma ApoE concentrations were related to CSF Aβ42, Tau and pTau levels and clinical characteristics in patients with subjective cognitive decline (n = 207) or mild cognitive impairment (n = 213) aged 64.2 ± 9.

Aminobisphosphonates inhibit dendritic cell-mediated antigen-specific activation of CD1d-restricted iNKT cells.

CD1d-restricted invariant natural killer T (iNKT) cells constitute an important immunoregulatory T cell subset that can be activated by the synthetic glycolipid α-galactosylceramide (α-GalCer) and initiate antitumor immune responses. As cancer patients are frequently treated with aminobisphosphonates (NBP), it is relevant to determine possible effects of NBP on CD1d-restricted glycolipid Ag-presentation to iNKT cells. We report a striking reduction of α-GalCer-induced iNKT cell activation by monocyte derived dendritic cells (moDC) upon their exposure to NBP during maturation.

Amyloid-β oligomer detection by ELISA in cerebrospinal fluid and brain tissue.

Amyloid-β (Aβ) deposits are important pathological hallmarks of Alzheimer's disease (AD). Aβ aggregates into fibrils; however, the intermediate oligomers are believed to be the most neurotoxic species and, therefore, are of great interest as potential biomarkers. Here, we have developed an enzyme-linked immunosorbent assay (ELISA) specific for Aβ oligomers by using the same capture and (labeled) detection antibody.

Direct downregulation of CNTNAP2 by STOX1A is associated with Alzheimer's disease.

STOX1A is a transcription factor which is functionally and structurally similar to the forkhead box protein family. STOX1A has been shown to be associated with pre-eclampsia, a pregnancy associated disease, and to have potential implications in late onset Alzheimer's disease. However, the exact function of STOX1A and its target genes are still largely unknown.

Whether, when and how chronic inflammation increases the risk of developing late-onset Alzheimer's disease.

Neuropathological studies have revealed the presence of a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) in Alzheimer's disease (AD) brains. These constituents of innate immunity are involved in several crucial pathogenic events of the underlying pathological cascade in AD, and recent studies have shown that innate immunity is involved in the etiology of late-onset AD. Genome-wide association studies have demonstrated gene loci that are linked to the complement system.

Innate immunity and the etiology of late-onset Alzheimer's disease.

Background: Neuropathological studies supported by experimental animal studies show that the constituents of the innate immunity are intimately involved in the early steps of the pathological cascade of Alzheimer's disease (AD).

Objectives: To show the evidence that constituents of the innate immunity contribute to the etiology of late-onset AD.

Methods: Evaluation of the relationship between the constituents of the innate immunity and genetic risk factors for late-onset AD.

Neuroinflammation - an early event in both the history and pathogenesis of Alzheimer's disease.

Background: About hundred years ago, Oskar Fischer proposed that the senile plaques are the consequence of the deposition of a foreign substance that could induce an inflammatory response leading to an abnormal neuritic response of the surrounding neurons.

Objectives: To show that the interest in inflammation in Alzheimer's disease (AD) is not only an early event in the history of AD but that inflammation is also an early event in the pathogenesis of AD.

Methods: Evaluation of the neuropathological, epidemiological and genetic evidence for a role of inflammation early in the pathogenesis of AD.

Variability in longitudinal cerebrospinal fluid tau and phosphorylated tau measurements.

Background: The influence of assay variation and duration of storage on changes in cerebrospinal fluid (CSF) levels of tau and phosphorylated (P)-tau with time was evaluated in 112 patients with various neurological disorders.

Methods: These patients (aged 66+/-9 years, 52% male), referred to our memory clinic, underwent two spinal taps (mean interval 19 months) and the baseline samples were assayed twice in a sandwich enzyme-linked immunosorbent assay (ELISA): once after the first spinal tap (A1) and once in a separately stored aliquot (A2) simultaneous with the follow-up sample (B).

Results: Coefficients of variances (CVs) of tau and P-tau levels determined in repeated spinal taps (DeltaB-A2) measured in one assay (10.

Neuroinflammation in plaque and vascular beta-amyloid disorders: clinical and therapeutic implications.

Background: The cerebral beta-amyloid (Abeta) disorders show a great variability in the distribution of parenchymal and vascular amyloid deposits.

Objective: To study the relationship between amyloid deposition and inflammatory responses in three distinct subtypes of cerebral Abeta disorders.

Methods: The distribution of inflammatory proteins and cells in vascular and plaque amyloid deposits was evaluated in postmortem brain tissue using immunohistochemistry.

Homogeneity of active demyelinating lesions in established multiple sclerosis.

Objective: Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS.

Small heat shock proteins associated with cerebral amyloid angiopathy of hereditary cerebral hemorrhage with amyloidosis (Dutch type) induce interleukin-6 secretion.

In hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), severe cerebral amyloid angiopathy (CAA) is associated with an inflammatory reaction. Small heat shock proteins (sHsps) are molecular chaperones and association of HspB8 with CAA in HCHWA-D has been observed. The aims of this study were to investigate (1) if other sHsps are associated with the pathological lesions in HCHWA-D brains, (2) if the amyloid-beta protein (A beta) increases production of sHsps in cultured cerebral cells and (3) if sHsps are involved in the cerebral inflammatory processes in both Alzheimer's disease (AD) and HCHWA-D.