Application of the WEPS and SWEEP models to non-agricultural disturbed lands.

Wind erosion not only affects agricultural productivity but also soil, air, and water quality. Dust and specifically particulate matter ≤10 µm (PM-10) has adverse effects on respiratory health and also reduces visibility along roadways, resulting in auto accidents. The Wind Erosion Prediction System (WEPS) was developed by the USDA-Agricultural Research Service to simulate wind erosion and provide for conservation planning on cultivated agricultural lands. A companion product, known as the Single-Event Wind Erosion Evaluation Program (SWEEP), has also been developed which consists of the stand-alone WEPS erosion submodel combined with a graphical interface to simulate soil loss from single (i.e., daily) wind storm events. In addition to agricultural lands, wind driven dust emissions also occur from other anthropogenic sources such as construction sites, mined and reclaimed areas, landfills, and other disturbed lands. Although developed for agricultural fields, WEPS and SWEEP are useful tools for simulating erosion by wind for non-agricultural lands where typical agricultural practices are not employed. On disturbed lands, WEPS can be applied for simulating long-term (i.e., multi-year) erosion control strategies. SWEEP on the other hand was developed specifically for disturbed lands and can simulate potential soil loss for site- and date-specific planned surface conditions and control practices. This paper presents novel applications of WEPS and SWEEP for developing erosion control strategies on non-agricultural disturbed lands. Erosion control planning with WEPS and SWEEP using water and other dust suppressants, wind barriers, straw mulch, re-vegetation, and other management practices is demonstrated herein through the use of comparative simulation scenarios. The scenarios confirm the efficacy of the WEPS and SWEEP models as valuable tools for supporting the design of erosion control plans for disturbed lands that are not only cost-effective but also incorporate a science-based approach to risk assessment.

Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease.

Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aß) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aß-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.

Prevalence of Submandibular Gland Synucleinopathy in Parkinson's Disease, Dementia with Lewy Bodies and other Lewy Body Disorders.

BACKGROUND: Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson's disease (PD). Here, we report on an extension of these studies to subjects with dementia with Lewy bodies (DLB) and other Lewy body disorders in 228 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders. OBJECTIVE: To provide an estimate of the prevalence of histological synucleinopathy in the submandibular glands of subjects with PD and other Lewy body disorders. METHODS: Submandibular gland sections from autopsied subjects were stained with an immunohistochemical method for α-synuclein phosphorylated at serine 129. Included were 146 cases with CNS Lewy-type synucleinopathy (LTS), composed of 46 PD, 28 DLB, 14 incidental Lewy body disease (ILBD), 33 Alzheimer's disease with Lewy bodies (ADLB) and 2 with progressive supranuclear palsy and Lewy bodies (PSPLB). Control subjects included 79 normal elderly, 15 AD, 12 PSP, 2 conticobasal degeneration (CBD) and 2 multiple system atrophy (MSA). RESULTS: Submandibular gland LTS was found in 42/47 (89%) of the PD subjects, 20/28 (71%) DLB, 4/33 (12%) ADLB and 1/9 (11%) ILBD subjects but none of the 110 control subjects. CONCLUSIONS: These results provide support for further clinical trials of in vivo submandibular gland diagnostic biopsy for PD and DLB. An accurate peripheral biopsy diagnosis would assist subject selection for clinical trials and could also be used to verify other biomarkers.

p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer's disease.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aß) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aß and mediates Aß-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aß. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aß deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aß deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing ß-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aß toxicity and would be a novel therapeutic target and biomarker for AD.

Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.

Multiple cellular systems exist to prevent uncontrolled inflammation in brain tissues; the suppressor of cytokine signaling (SOCS) proteins have key roles in these processes. SOCS proteins are involved in restricting cellular signaling pathways by enhancing the degradation of activated receptors and removing the stimuli for continued activation. There are eight separate SOCS genes that code for proteins with similar structures and properties. All SOCS proteins can reduce signaling of activated transcription factors Janus kinase (JAK) and signal transducer and activator of transcription (STAT), but they also regulate many other signaling pathways. SOCS-1 and SOCS-3 have particular roles in regulating inflammatory processes. Chronic inflammation is a key feature of the pathology present in Alzheimer's disease (AD)-affected brains resulting from responses to amyloid plaques or neurofibrillary tangles, the pathological hallmarks of AD. The goal of this study was to examine SOCS gene expression in human non-demented (ND) and AD brains and in human brain-derived microglia to determine if AD-related pathology resulted in a deficit of these critical molecules. We demonstrated that SOCS-1, SOCS-2, SOCS-3 and cytokine-inducible SH2 containing protein (CIS) mRNA expression was increased in amyloid beta peptide (Aß)- and inflammatory-stimulated microglia, while SOCS-6 mRNA expression was decreased by both types of treatments. Using human brain samples from the temporal cortex from ND and AD cases, SOCS-1 through SOCS-7 and CIS mRNA and SOCS-1 through SOCS-7 protein could be detected constitutively in ND and AD human brain samples. Although, the expression of key SOCS genes did not change to a large extent as a result of AD pathology, there were significantly increased levels of SOCS-2, SOCS-3 and CIS mRNA and increased protein levels of SOCS-4 and SOCS-7 in AD brains. In summary, there was no evidence of a deficit of these key inflammatory regulating proteins in aged or AD brains.

What happens to microglial TREM2 in Alzheimer's disease: Immunoregulatory turned into immunopathogenic?

Microglia play major roles in initiation, coordination and execution of innate immunity in the brain. In the adult brain, these include maintenance of homeostasis, neuron and tissue repair, and eliminating infectious agents, apoptotic cells, and misfolded proteins. Some of these activities are accompanied by inflammatory reactions; and others are performed with no inflammatory effects. Under normal conditions, triggering receptor expressed on myeloid cells 2 (TREM2) belongs to the second category. It pairs with the adaptor protein DNAX-activating protein of 12kDa (DAP12) to induce phagocytosis of apoptotic neurons without inflammatory responses, and to regulate Toll-like receptor-mediated inflammatory responses, and microglial activation. Although ligands for TREM2 are largely unknown, the mitochondrial heat shock protein 60, expressed on cell surface of apoptotic neurons, is a specific ligand that activates TREM2-mediated phagocytosis by microglia. TREM2 also phagocytoses amyloid beta peptide in cultured cells. Several TREM2 mutations have been identified recently that increase the risk of Alzheimer's disease, Frontotemporal dementia, Parkinson's disease, and amyotrophic lateral sclerosis. Some of these mutations cause impaired proteolysis of full-length TREM2 at the plasma membrane to different degrees. The defects in the intramembrane cleavage result in dysfunction of phagocytosis signaling. The association of TREM2 mutations with neurodegenerative disease also calls for the understanding of the biology and pathological role of non-mutated TREM2 on human brains and microglia. This review provides a summary of current literature in TREM2 and DAP12 from several aspects, and proposes a theory that loss of TREM2 functions might contribute to the immunopathogenic role of microglia in Alzheimer's disease.

Modelling the impact of HIV prevention and treatment for men who have sex with men on HIV epidemic trajectories in low- and middle-income countries.

Little is known about the impact of combination HIV prevention interventions for men who have sex with men (MSM) and the impacts on the wider epidemics. Modelling analyses of MSM-specific interventions across varied HIV epidemics may inform evidence-based responses. The Goals model was adapted to project the impacts of providing HIV interventions for MSM and access to expanded coverage of antiretroviral therapy (ART) for adults to measure the effects on the MSM and adult epidemics in Peru, Ukraine, Kenya and Thailand. Positive impacts were observed in all four countries. Across epidemics, 14-25% of infections among MSM may be averted between 2012 and 2016 when MSM interventions are brought to scale and MSM have equal access to expanded ART for adults. Among adults, MSM interventions may avert up to 4000 new infections, in addition to the benefits associated with increased ART. Greatest impacts from expanded interventions were observed in countries where same sex transmission contributes significantly to the HIV epidemic. While significant benefits are observed among the adult and MSM populations with expansion of ART, consideration should be given to the synergies of combining ART expansion with targeted interventions to reach hidden, high-risk populations for HIV testing and counselling and linkages to care.

Consequences of Aberrant Insulin Regulation in the Brain: Can Treating Diabetes be Effective for Alzheimer's Disease.

There is an urgent need for new ways to treat Alzheimer's disease (AD), the most common cause of dementia in the elderly. Current therapies are modestly effective at treating the symptoms, and do not significantly alter the course of the disease. Over the years, a range of epidemiological and experimental studies have demonstrated interactions between diabetes mellitus and AD. As both diseases are leading causes of morbidity and mortality in the elderly and are frequent co-morbid conditions, it has raised the possibility that treating diabetes might be effective in slowing AD. This is currently being attempted with drugs such as the insulin sensitizer rosiglitazone. These two diseases share many clinical and biochemical features, such as elevated oxidative stress, vascular dysfunction, amyloidogenesis and impaired glucose metabolism suggesting common pathogenic mechanisms. The main thrust of this review will be to explore the evidence from a pathological point of view to determine whether diabetes can cause or exacerbate AD. This was supported by a number of animal models of AD that have been shown to have enhanced pathology when diabetic conditions were induced. The one drawback in linking diabetes and insulin to AD has been the postmortem studies of diabetic brains demonstrating that AD pathology was not increased; in fact decreased pathology has often been reported. In addition, diabetes induces its own distinct features of neuropathology different from AD. There are common pathological features to be considered including vascular abnormalities, a major feature arising from diabetes; there is increasing evidence that vascular abnormalities can contribute to AD. The most important common mechanism between insulin-resistant (type II) diabetes and AD could be impaired insulin signaling; a form of toxic amyloid can damage neuronal insulin receptors and affect insulin signaling and cell survival. It has even been suggested that AD could be considered as "type 3 diabetes" since insulin can be produced in brain. Another common feature of diabetes and AD are increased advanced glycation endproduct-modified proteins are found in diabetes and in the AD brain; the receptor for advanced glycation endproducts plays a prominent role in both diseases. In addition, a major role for insulin degrading enzyme in the degradation of Aß peptide has been identified. Although clinical trials of certain types of diabetic medications for treatment of AD have been conducted, further understanding the common pathological processes of diabetes and AD are needed to determine whether these diseases share common therapeutic targets.

Quantification of condylar resorption in temporomandibular joint osteoarthritis.

OBJECTIVE: This study was performed to determine the condylar morphologic variation of osteoarthritic (OA) and asymptomatic temporomandibular joints (TMJs) and to determine its correlation with pain intensity and duration. STUDY DESIGN: Three-dimensional surface models of mandibular condyles were constructed from cone-beam computerized tomography images of 29 female patients with TMJ OA (Research Diagnostic Criteria for Temporomandibular Disorders group III) and 36 female asymptomatic subjects. Shape correspondence was used to localize and quantify the condylar morphology. Statistical analysis was performed with multivariate analysis of covariance analysis, using Hotelling T(2) metric based on covariance matrices, and Pearson correlation. RESULTS: The OA condylar morphology was statistically significantly different from the asymptomatic condyles (P < .05). Three-dimensional morphologic variation of the OA condyles was significantly correlated with pain intensity and duration. CONCLUSION: Three-dimensional quantification of condylar morphology revealed profound differences between OA and asymptomatic condyles, and the extent of the resorptive changes paralleled pain severity and duration.

A novel rat model for glioblastoma multiforme using a bioluminescent F98 cell line.

In experimental neuro-oncology there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for glioblastoma multiforme (GBM). Rat models have remained the mainstay of neuro-oncology research for over 30 years; however, despite extensive experimentation, there is no one rat model that truly reflects the features of human tumours. We have developed a novel rat brain tumour model that closely resembles human GBM in biological behaviour and that utilizes bioluminescence imaging (BLI) to follow day-to-day in vivo progress of the tumour. F98 glioma cells were transfected with the firefly luciferase gene and injected orthotopically into the brains of 24 rats. Weekly BLI after subcutaneous injection of luciferin allowed for in vivo monitoring of the progress of the brain tumours. Euthanasia and histological analysis of the rodent brains at varying stages post-implantation, allowed for statistically significant correlation between tumour size and luminescence (p=0.002). The utility of this model is readily apparent, allowing us a way of examining the effects of new and novel therapeutics in these rats.

Rotavirus vaccination for Hong Kong children: an economic evaluation from the Hong Kong Government perspective.

AIMS: To perform an economic analysis of government-funded universal rotavirus vaccination in Hong Kong from the government's perspective. METHODS: A Markov model of costs and effects (disability averted) associated with universal vaccination was compared with no vaccination. In both strategies, newborns were studied until 5 years of age or until they died, using cost, probability and utility data from the literature. The potential cost savings and cost effectiveness of vaccination were calculated and their sensitivities to changes in vaccine and health care costs, presumed decline in vaccine efficacy over time, and the use of discounting and age weights were determined. RESULTS: Depending on assumptions, the new rotavirus vaccines would be cost saving to the Hong Kong Government if they cost less than US$40-92 per course. Higher vaccine costs would quickly lead to an incremental cost-effectiveness ratio exceeding that of the gross national product per capita if the mortality rate of rotavirus gastroenteritis remained at zero. CONCLUSIONS: Based on 2002 demographic, cost and morbidity data and reasonable uncertainty estimates of these variables, a universal rotavirus vaccination programme paid for by the Hong Kong Government is cost neutral at a per course vaccine cost of US$40-92. For a fixed vaccine cost, the potential savings and cost effectiveness of the vaccine increase with higher estimated health care costs and vice versa.

Can a "novice" do aneurysm surgery? Surgical outcomes in a low-volume, non-subspecialised neurosurgical unit.

The objective of this paper is to review the results of a junior general neurosurgeon performing aneurysm surgery and compare these to the remainder of his low-volume unit. Prospectively collected data was analysed for 114 aneurysms clipped in 99 patients between July 2001 and May 2005. Overall there was a 0.9% mortality rate and 10.8% complication rate. The favourable outcome rate for the unit was 100% for unruptured aneurysms, 90.4% for grades 1-3 patients and 30% for poor grade patients (grades 4 and 5). The novice neurosurgeon had no mortality and a favourable outcome rate of 94.7% for grades 1-3 patients and 50% for poor grade patients. Acceptable results can be obtained with cerebral aneurysm surgery in a low-volume centre by Australian-trained, non-subspecialty neurosurgeons.

Preventing activation of receptor for advanced glycation endproducts in Alzheimer's disease.

Receptor for advanced glycation endproducts (RAGE), a member of the immunoglobulin superfamily, is a multi-ligand, cell surface receptor expressed by neurons, microglia, astrocytes, cerebral endothelial cells, pericytes, and smooth muscle cells. At least three major types of the RAGE isoforms (full length, C-truncated, and N-truncated) are present in human brains as a result of alternative splicing. Differential expression of each isoform may play a regulatory role in the physiological and pathophysiological functions of RAGE. Analysis of RAGE expression in non-demented and Alzheimer's disease (AD) brains indicated that increases in RAGE protein and percentage of RAGE-expressing microglia paralleled the severity of disease. Ligands for RAGE in AD include amyloid beta peptide (Abeta), S100/calgranulins, advanced glycation endproduct-modified proteins, and amphoterin. Collective evidence from in vitro and in vivo studies supports that RAGE plays multiple roles in the pathogenesis of AD. The major features of RAGE activation in contributing to AD result from its interaction with Abeta, from the positive feedback mechanisms driven by excess amounts of Abeta, and combined with sustained elevated RAGE expression. The adverse consequences of RAGE interaction with Abeta include perturbation of neuronal properties and functions, amplification of glial inflammatory responses, elevation of oxidative stress and amyloidosis, increased Abeta influx at the blood brain barrier and vascular dysfunction, and induction of autoantibodies. In this article, we will review recent advances of RAGE and RAGE activation based on findings from cell cultures, animal models, and human brains. The potential for targeting RAGE mechanisms as therapeutic strategies for AD will be discussed.

Investigations with cultured human microglia on pathogenic mechanisms of Alzheimer's disease and other neurodegenerative diseases.

Inflammation-mediated mechanisms for human neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) have evolved from being on the fringe of medical hypotheses to mainstream thinking. Pioneering immunopathology studies with human brain tissues identified microglia associated with neuropathologic hallmarks of these diseases. As activated macrophages were known to produce many potential toxic products, this gave rise to the hypothesis that activated microglia (brain resident macrophages) could be contributing to the degeneration of key target neurons in these diseases, as well as potential vascular dysfunction. Studies with microglia derived from different sources, including human brains, have confirmed that activated microglia can mediate neuronal cell death. Based on these theories, a number of human clinical trials with antiinflammatory agents have been carried out on AD patients. Results to date have indicated a lack of effectiveness at slowing disease progression and have begun to cast doubt on the significance of inflammation in AD. It has been shown recently that activating microglia through immunization of amyloid plaque-developing mice with amyloid beta peptide (Abeta) has promise as a therapeutic strategy and despite some setbacks, has potential as a treatment for AD patients. This article will consider experimental data with microglia to determine whether the additional targets need to be investigated. The use of human microglia cultures, in particular those derived from elderly diseased human brains, offers an experimental system that can closely model the cell type activated in human neurodegenerative diseases. Experimental data produced by our laboratory and others is reviewed to determine the contribution of this unique experimental model to understanding disease mechanisms and possibly discovering new therapeutic targets.

Stereotactic atlantoaxial transarticular screw fixation.

Atlantoaxial stabilisation can be performed using a variety of surgical techniques. Developments in spinal instrumentation and stereotactic technology have been incorporated into these procedures. We have recently adopted frameless stereotaxy to assist in such operations. A retrospective study of patients treated by the authors and using frameless stereotaxy from 2001 to 2002 was performed. Each patient underwent pre-operative fine-cut CT in the position of fixation. Using these images, screw trajectory was planned. Stereotaxis and fluoroscopy was utilised during fixation. A post-operative CT was performed. There were nine patients. Bilateral screw placement was achieved in eight. In the remaining case stereotactic planning predicted the single screw fixation. There were no post-operative complications. Post-operative CT showed screw placement corresponding to the planned trajectory in all 17 screws. Stabilisation was achieved in all. Stereotactic atlantoaxial screw fixation is an accessible, safe and accurate method for the management of C1-2 instability.

Preliminary study of shunt related death in paediatric patients.

Hydrocephalus is a condition commonly encountered in paediatric and adult neurosurgery and cerebrospinal fluid (CSF) shunting remains the treatment of choice for many cases. Despite improvements in shunt technology and technique, morbidity and mortality remain. The incidence of early shunt obstruction is high with later failures seen less frequently. This review aims to examine mortality associated with mechanical failure of CSF shunts within Queensland. Neurosurgical and Intensive Care databases were reviewed for cases of mortality associated with shunt failure. Eight cases were identified between the years of 1992 and 2002 with the average age at death 7.7 years. Deaths occurred on average 2 years after last shunt revision. Seven of the eight patients lived outside the metropolitan area. Shunting remains an imperfect means of treating hydrocephalus. Mortality may be encountered at any time post surgery and delays to surgical intervention influence this. Alternative measures such as third ventriculostomy or the placement of a separate access device should be considered. In the event of emergency, a spinal needle could be used to access the ventricle along the course of the ventricular catheter.

Refractory headache due to spontaneous intracranial hypotension from a CSF leak at C1-2.

A case of spontaneous intracranial hypotension presenting with refractory headaches is reported. After exhaustive investigation, the cause of the patient's symptoms was found to be spontaneous leak of CSF at the C1-2 level. The patient underwent surgical repair of the CSF leak and made a good recovery. This case represents a typical presentation of a rare condition. The investigation and treatment of this condition is discussed.

Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine.

Overproduction of the peptide amyloid beta (Abeta) is thought to be a critical pathogenetic event in Alzheimer's disease (AD). Decreasing A production may therefore slow or halt the progression of AD. In vitro work has indicated that cholinergic muscarinic receptor agonists may reduce cellular production of Abeta. Here we show that systemic administration of physostigmine, an acetylcholinesterase inhibitor, lowers Abeta levels in vivo. Guinea pigs treated for 10 days with s.c. physostigmine had levels of cortical AbetaN-40 and N-42 which were 57% and 72%, respectively, of those in control animals. Levels of cortical beta-amyloid precursor protein were not significantly affected by drug treatment. These results suggest that cholinergic therapy may affect the course of AD by limiting Abeta accumulation.

Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: identification of a cellular activation mechanism.

Receptor-mediated interactions with amyloid beta-peptide (Abeta) could be important in the evolution of the inflammatory processes and cellular dysfunction that are prominent in Alzheimer's disease (AD) pathology. One candidate receptor is the receptor for advanced glycation endproducts (RAGE), which can bind Abeta and transduce signals leading to cellular activation. Data are presented showing a potential mechanism for Abeta activation of microglia that could be mediated by RAGE and macrophage colony-stimulating factor (M-CSF). Using brain tissue from AD and nondemented (ND) individuals, RAGE expression was shown to be present on microglia and neurons of the hippocampus, entorhinal cortex, and superior frontal gyrus. The presence of increased numbers of RAGE-immunoreactive microglia in AD led us to further analyze RAGE-related properties of these cells cultured from AD and ND brains. Direct addition of Abeta(1-42) to the microglia increased their expression of M-CSF. This effect was significantly greater in microglia derived from AD brains compared to those from ND brains. Increased M-CSF secretion was also demonstrated using a cell culture model of plaques whereby microglia were cultured in wells containing focal deposits of immobilized Abeta(1-42). In each case, the Abeta stimulation of M-CSF secretion was significantly blocked by treatment of cultures with anti-RAGE F(ab')2. Treatment of microglia with anti-RAGE F(ab')2 also inhibited the chemotactic response of microglia toward Abeta(1-42). Finally, incubation of microglia with M-CSF and Abeta increased expression of RAGE mRNA. These microglia also expressed M-CSF receptor mRNA. These data suggest a positive feedback loop in which Abeta-RAGE-mediated microglial activation enhances expression of M-CSF and RAGE, possibly initiating an ascending spiral of cellular activation.