[Show abstract][Hide abstract] ABSTRACT: Patients with Parkinson's disease (PD) have a heightened risk of sustaining hip fractures due to disturbed balance and gait insecurity. This study aims to determine the impact of PD on the perioperative course and medium-term functional outcome of patients with hip fractures.
A total of 402 hip fracture patients, aged ≥60 years, were prospectively enrolled. On admission, the American Society of Anesthesiologists score, Mini-Mental Status Examination, and Barthel Index (BI), among other scales, were documented. The Hoehn and Yahr scale was used to assess the severity of PD. The functional outcome was assessed by performance on the BI, Tinetti test (TT), and Timed Up and Go test (TUG) at discharge and at the 6-month follow-up. Additionally, the length of hospitalization, perioperative complications, and discharge management were documented. A multivariate regression analysis was performed to control for influencing factors.
A total of 19 patients (4.7 %) had a concomitant diagnosis of PD. The functional outcome (BI, TT, and TUG) was comparable between groups (all p > 0.05). Grade II (52.6 vs. 26.1 %; OR = 4.304, p = 0.008) and IV complications (15.8 vs. 4.4 %; OR = 7.785, p = 0.012) occurred significantly more often among PD patients. While the diagnosis of PD was associated with a significantly longer mean length of hospital stay (β = 0.119, p = 0.024), the transfer from acute hospital care showed no significant difference (p = 0.246). Patients with an additional diagnosis of PD had inferior results in BI at the 6-month follow-up (p = 0.038).
PD on hospital admission is not an independent risk factor for in-hospital mortality or an inferior functional outcome at hospital discharge. However, patients with PD are at risk for specific complications and longer hospitalization at the time of transfer from acute care so as for reduced abilities in activities of daily living in the medium term.
Archives of Orthopaedic and Trauma Surgery 08/2015; 135(11). DOI:10.1007/s00402-015-2298-3 · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of the present study was to determine the independent factors influencing mobilization progress after geriatric hip fractures.
Patients and methods:
392 Hip fracture patients older than 60 years were included in this prospective, observational, cohort study. The progress of mobilization was measured with walking ability 4 days post-surgery, ability to climb stairs until discharge and the Tinetti test at discharge. Factors correlated with the progress of mobilization were determined using multivariate analyses.
The independent factors influencing walking ability 4 days post-surgery were the pre-fracture Charlson Comorbidity Index (OR=0.834, p=0.005), the American Society of Anesthesiologists Score (OR=0.550, p=0.013), pre-fracture Barthel Index ([BI], OR=1.019, p=0.012) and risk for depression, as measured by the Geriatric Depression Scale, (OR=0.896, p=0.013). The probability of climbing stairs until discharge was influenced by the patient's age (OR=0.840, p<0.001), pre-fracture BI (OR=1.047, p=0.042), cognitive impairment, as measured by the mini mental state examination (OR=1.182 p=0.008), pre surgical hemoglobin (OR=1.026, p=0.044), time until surgery (OR=0.961, p=0.023), duration of surgery (OR=0.982, p=0.014), and surgery type (prosthesis, OR=4.545, p=0.001). Similar variables influenced the Tinetti test ad discharge.
While pre-fracture co-morbidities and function cannot be changed, the treatment of patients with cognitive impairment and depressive symptoms should be optimized. Efforts should be undertaken to ensure early surgery for all hip fractures.
Archives of Gerontology and Geriatrics 02/2015; 60(3). DOI:10.1016/j.archger.2015.01.017 · 1.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To prospectively determine health status and health utility and its predictors in patients with multiple sclerosis (MS).
A total of 144 MS patients (mean age: 41.0 +/-11.3y) with different subtypes (patterns of progression) and severities of MS were recruited in an outpatient university clinic in Germany. Patients completed a questionnaire at baseline (n = 144), 6 months (n = 56) and 12 months (n = 55). Health utilities were assessed using the EuroQol instrument (EQ-5D, EQ VAS). Health status was assessed by several scales (Expanded Disability Severity Scale (EDSS), Modified Fatigue Impact Scale (M-FIS), Functional Assessment of MS (FAMS), Beck Depression Inventory (BDI-II) and Multiple Sclerosis Functional Composite (MSFC)). Additionally, demographic and socioeconomic parameters were assessed. Multivariate linear and logistic regressions were applied to reveal independent predictors of health status.
Health status is substantially diminished in MS patients and the EQ VAS was considerably lower than that of the general German population. No significant change in health-status parameters was observed over a 12-months period. Multivariate analyses revealed M-FIS, BDI-II, MSFC, and EDSS to be significant predictors of reduced health status. Socioeconomic and socio-demographic parameters such as working status, family status, number of household inhabitants, age, and gender did not prove significant in multivariate analyses.
MS considerably impairs patients' health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome.
Health and Quality of Life Outcomes 10/2013; 11(1):162. DOI:10.1186/1477-7525-11-162 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Parkinson's disease (PD) is associated with neurodegeneration of dopaminergic neurons and an accompanying neuroinflammatory process in the substantia nigra (SN). The cholinergic anti-inflammatory signalling pathway allows the autonomic nervous system to modulate immunologic stimuli and inflammatory processes. A major component of this pathway is the α7 nicotinic acetylcholine receptor (α7 nACh receptor), which is expressed on immune cells such as microglia. Objective: To determine the role of this cholinergic anti-inflammatory signalling pathway, we investigated the effects of the selective α7 nACh agonist PNU-282987 and of the non-competitive nACh antagonist mecamylamine on microglia-induced neuroinflammation and toxin-induced degeneration of dopaminergic neurons in a mouse model of PD. Methods: PNU-282987, mecamylamine or placebo administration was started one day before MPTP intoxication and repeated daily until sacrifice after MPTP intoxication. C57Bl/6 mice were injected intraperitoneally four times at 2 h intervals with either 20 mg/kg MPTP-HCl or a corresponding volume of saline. Two or seven days after the end of the MPTP intoxication, the animals were killed and their brains were processed for further analysis. Results: Treatment with PNU-282987 resulted in an attenuation of neuroinflammation in the MPTP-lesioned SN. Furthermore, PNU-282987 attenuated MPTP-induced dopaminergic cell loss in the SN and reduced striatal dopamine depletion. Unexpectedly, mecamylamine lowered neuroinflammation as well, though it did not show a neuroprotective potential at the nigral level. Conclusions: Our results demonstrate the therapeutic potential of the selective α7 nicotinic acetylcholine agonist PNU-282987 in attenuating neuroinflammation and toxin-induced loss of dopaminergic neurons in the acute MPTP mouse model of PD.
[Show abstract][Hide abstract] ABSTRACT: Hip fractures are associated with reduced health-related quality of life (HrQoL). We found pre-existing need of care or limited function, cognitive impairment, and depression to be independent factors associated with lower HrQoL during the postsurgical period. In contrast, joint replacement was associated with better HrQoL compared to internal fixation. Patients' treatment should be focused on functional recovery and treatment of depression. INTRODUCTION: The aim of the study was to identify independent factors that were correlated with health-related quality of life (HrQoL) after hip fracture. METHODS: A total of 402 patients with a mean age of 81 years suffering from a hip fracture were included in this prospective, observational cohort study. HrQoL (determined by the EuroQol instrument) was measured at admission and at discharge from an acute care hospital. Independent factors correlated with HrQoL at discharge and changes from pre-fracture to discharge were determined using multivariate analyses. The influence of antidepressants was evaluated by an ANOVA with repeated measurements. RESULTS: Need of care prior to fracture was the most important determinant of EQ-5D index at discharge (ß = -0.359, p = 0.003). Additionally, low Mini Mental Status Examination (MMSE) was associated with a lower EQ-5D index at discharge (MMSE 0-9: ß = -0.238, p <0.001; MMSE 10-19: ß = -0.294, p <0.001) and a greater decrease in EQ-5D during hospitalisation (MMSE 10-19: ß = 0.281, p <0.001), while joint replacement (compared to internal fixation) was associated with a higher EQ-5D index (ß = 0.188, p = 0.002) and a lower decrease in the index (ß = -0.216, p = 0.003). EQ VAS values at discharge were correlated with pre-fracture Barthel Index (ß = 0.253, p <0.001) and Geriatric Depression Scale scores (ß = -0.135, p = 0.026). Depressive patients on antidepressants demonstrated less of a decrease in the EQ-5D index compared to patients not receiving medication (F = 2.907, p = 0.090). CONCLUSIONS: Acute care of hip fracture patients should be focused on functional recovery and treatment of depression. When the preferred surgical strategy is unclear, joint replacement should be considered.
Osteoporosis International 06/2013; 25(2). DOI:10.1007/s00198-013-2415-5 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hip fractures are common geriatric fractures with increasing incidence. Treatment of these fractures is still associated with high rates of complications and poor outcome. Data concerning unexpected re-admission to a Level 2 unit after an initial inconspicuous postoperative course are limited. We aimed to identify causes and associated risk factors for admission as well as impact of re-admission on acute care and short-term outcome.
Patients over 60 years of age with hip fractures were included in this prospective single-centre observational study. Patients with polytrauma or malignancy-associated fractures were excluded. Age, gender, fracture type, pre-fracture residential, physical and cognitive status, recording to the American Society of Anesthesiologists (ASA) score, Barthel Index (BI) and Mini-Mental State Examination (MMSE) were recorded on admission. Date, type of surgery and operation time were evaluated. Postoperatively, the prevalence of and reasons for unexpected re-admission to the Level 2 unit and patients' outcome were measured. Parameters were hospital mortality, BI at discharge, length of stay in hospital and type of discharge. Univariate and multivariate analyses were performed to identify risk factors for admission to the Level 2 unit and influence on patients' outcome.
Out of 402 included patients, 48 (12%) were re-admitted to the Level 2 unit. The most frequent reasons were non-surgical (n=38), such as respiratory failure (n=12), cardiovascular diseases (n=8) and acute renal failure (n=5). Ten patients were re-admitted due to a revision surgery of the hip. We identified two independent risk factors for readmission: male gender (odds ratio (OR)=2.38, confidence interval (95% CI)=1.10-5.15, p=0.027) and type of fracture, especially femoral neck fracture (OR=7.40, 95% CI=2.39-23.26, p=0.001). Patients who were re-admitted to the Level 2 unit had a higher mortality (β=2.09, OR=8.07, 95% CI=2.44-26.75, p=0.001), an increase in hospital stay (β=7.0, 95% CI 5.2-8.7, p<0.001) and a lower functional outcome (BI, β=-17, 95% CI=-23 to -10, p<0.001).
Unexpected admission to the Level 2 unit in the post-surgical period is a frequent phenomenon in geriatric hip-fracture patients. Males and femoral neck fracture patients seem to be especially endangered. Although the majority of reasons for admissions were not immediately life-threatening illnesses, they had a substantial negative impact on patients' outcome. This emphasises the importance of careful handling of this frail patient population.
[Show abstract][Hide abstract] ABSTRACT: Background
Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates.
Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models.
The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models.
The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.
Health and Quality of Life Outcomes 03/2013; 11(1):35. DOI:10.1186/1477-7525-11-35 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bei proximalen Femurfrakturen wird nach den aktuellen Leitlinien eine frühzeitige operative Therapie empfohlen. Problematisch ist dabei das Management einer gerinnungshemmenden Vormedikation. Ziel war die Evaluation der diesbezüglichen klinikinternen SOP (,,standard operating procedure“).Alle geriatrischen Patienten mit proximaler Femurfraktur wurden prospektiv in die Studie aufgenommen. Neben der vorbestehenden gerinnungshemmenden Medikation wurden die Hb-Werte bei Aufnahme und Entlassung, Zeitpunkt und Dauer der Operation, die Transfusionsrate sowie systemische und lokale Komplikationen erfasst.Bei 154 (62%) der eingeschlossenen 247 Patienten bestand eine gerinnungshemmende Vormedikation. Patienten, die Acetylsalicylsäure (ASS) einnahmen, wurden häufiger transfundiert [62%, 95%-Konfidenzintervall (95%-KI) =53–72%; pBei Behandlung nach unserer SOP scheint eine gerinnungshemmende Medikation keinen Einfluss auf die Komplikationsrate nach proximaler Femurfraktur zu haben. Die höhere Transfusionsrate bei ASS-Medikation kann mit frühzeitiger Transfusion erklärt werden. Marcumar® mit Konakion zu antagonisieren führt zwar zu einer späteren Operation, scheint jedoch ebenfalls ausreichend. Eine Analyse mit höherer Patientenzahl über eine längere Periode sollte angeschlossen werden.
Der Unfallchirurg 01/2013; 116(10). · 0.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Under current guidelines surgical care of hip fractures has to be initiated within 48 h which is a challenge for the management of patients on medical anticoagulation. The aim of this study was to evaluate the in-house standard operation procedure (SOP) concerning these patients.
All geriatric hip fracture patients were included in this prospective study. Data concerning medical anticoagulation and hemoglobin levels on admission and at discharge, the start and duration of surgery, transfusion rates and postoperative complications were collected
A total of 154 (62%) out of 247 patients were on anticoagulants. Patients on acetylsalicylic acid (ASA) demonstrated a significant increase in the rate of transfusion (62%, 95% CI, range 53%-72%, p<0.05) but lost significantly less hemoglobin during hospitalization (1.25 g/dl, 95% CI 0.62-1.88g/dl, p<0.05) in comparison to the control group (40% transfused, hemoglobin loss 3.00 g/dl). Patients on phenprocoumon were operated on later (26 h versus 20 h,95% CI 22-30, p<0.001). There were no significant differences concerning complications.
Under this SOP anticoagulation has no impact on complication rates after hip fracture. The increased transfusion rates under ASS can be attributed to early blood transfusions. Antagonization of coumarin with vitamin K delays surgery but seems adequate. An analysis of more patients over a longer period of time should be conducted.
Der Unfallchirurg 06/2012; 116(10). DOI:10.1007/s00113-012-2235-7 · 0.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nationwide analyses of drug use can provide a prevalence estimate of the underlying disease and can help in understanding the characteristics of treatment. This study aimed for such analyses regarding the utilization of antiepileptic drugs (AED) for epilepsy in Germany. In 2009, all 4,115,705 AED prescriptions of all German patients with statutory health insurance (70,011,508 persons) were retrospectively analyzed. The IMS(®) LRx database served as data source, which accesses nationwide pharmacy data centers processing all German prescription data. To establish the age and sex-specific percentage of patients taking AED because of epilepsy, we used a second database, Disease Analyzer(®), which covered a representative sample of the German population (7.2 million patients) and contained ICD10 codes alongside with prescription data. The period prevalence of patients taking AED because of epilepsy was 9.1/1,000 (children/adolescents: 5.2/1,000; elderly: 12.5/1,000). Of the patients, 83.1 % took at least one of four AED: valproate (29.8 %), carbamazepine (26.4 %), lamotrigine (21.4 %), and levetiracetam (16.9 %). Oxcarbazepine and sultiame were popular with pediatricians. Elderly patients frequently received phenytoin and primidone. More than half of the patients were treated by family physicians; 68 % took AED in monotherapy and 7.9 % received >2 AED (children/adolescents: 12.5 %). The costs for AED prescribed for epilepsy amounted to 285.1 Mio (median AED costs/patient: 158/a). The German 2009 prevalence of epileptic patients taking AED was 9.1/1,000. Family physicians cared for the majority of patients. Prevalence and prescribing patterns changed with age. Costs of AED against epilepsy added up to 1 % of total medication costs in Germany.
Journal of Neurology 04/2012; 259(11). DOI:10.1007/s00415-012-6509-3 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. In the later (advanced) stages of PD, the initial treatment of early PD becomes less effective and long-term side effects of dopaminergic treatment become apparent. In advanced PD, motor and non-motor complications occur, which increase treatment costs. Increasing disability and impaired activities of daily living concomitantly raise indirect costs, due to loss in productivity. Hence, the economic burden of advanced PD is substantial for both the society and the patients with their caregivers. AREAS COVERED: A systematic literature search was performed involving the databases NHS CRD (National Health Service Centre for Reviews and Dissemination) and PubMed until July 15, 2011. "Parkinson" [Mesh] and "cost" were used as search terms in PubMed and only "Parkinson" in the CRD database. EXPERT OPINION: Economic evaluations are scarce and heterogeneous, and their interpretation may be limited due to methodological shortcomings. Dopamine agonists, COMT and MAO-B inhibitors as well levodopa infusion and deep brain stimulation are reported to be cost-effective in the respective decision frameworks. However, these results are heavily dependent on assumptions of drug costs and effect sizes used in the models. More detailed real-life information from long-term clinical trials is needed to feed the economic models, especially for head-to-head comparisons. To date, no economic evaluation has been undertaken for possible neuroprotective/disease modifying effects, and further research is needed for evaluations of interventions for non-motor symptoms.
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons of the substantia nigra pars compacta with unknown aetiology. 6-Hydroxydopamine (6-OHDA) treatment of neuronal cells is an established in vivo model for mimicking the effect of oxidative stress found in PD brains. We examined the effects of 6-OHDA treatment on human neuroblastoma cells (SH-SY5Y) and primary mesencephalic cultures. Using a reverse arbitrarily primed polymerase chain reaction (RAP-PCR) approach we generated reproducible genetic fingerprints of differential expression levels in cell cultures treated with 6-OHDA. Of the resulting sequences, 23 showed considerable homology to known human coding sequences. The results of the RAP-PCR were validated by reverse transcription PCR, real-time PCR and, for selected genes, by Western blot analysis and immunofluorescence. In four cases, [tomoregulin-1 (TMEFF-1), collapsin response mediator protein 1 (CRMP-1), neurexin-1, and phosphoribosylaminoimidazole synthetase (GART)], a down-regulation of mRNA and protein levels was detected. Further studies will be necessary on the physiological role of the identified proteins and their impact on pathways leading to neurodegeneration in PD.
[Show abstract][Hide abstract] ABSTRACT: To estimate costs of multiple sclerosis (MS) in a German cohort according to severity of the disease and clinical symptoms.
144 patients were recruited from an MS outpatient clinic. Costs were calculated according to current German health-economic guidelines from the perspective of the social health insurance system. Patients were either interviewed or completed a questionnaire. Cost assessment covered a 3-month period. Health outcomes were: Expanded Disability Status Scale, MS Functional Composite, Functional Assessment of MS, fatigue, depression (Beck Depression Inventory II) and patients' socioeconomic status. Multivariate linear regression identified independent cost predictors.
Total quarterly costs per patient were EUR 10,329 (95% CI 9,357-11,390). Direct costs were EUR 5,344 for the social health insurance system and EUR 140 for the patient. Drugs represented the major share of direct costs (and 35% of total costs); indirect costs accounted for 47% of total costs. Univariate and multivariate analyses identified age, disability, fatigue and depression as independent predictors for total, indirect or drug costs.
MS represents a high economic burden, with direct costs exceeding indirect costs. To reduce costs, research should focus on prevention that slows down progression of MS. Rehabilitation and symptomatic treatment may have merits in decreasing indirect costs.
European Neurology 11/2011; 66(6):311-21. DOI:10.1159/000331043 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. Methods/Design: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45–80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients’ functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. Results: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 ± 7.9 years, with a mean disease duration of 6.8 ± 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. Conclusion: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE.
[Show abstract][Hide abstract] ABSTRACT: Amyloid-β (Aβ) oligomer toxicity is a crucial factor in the development of Alzheimer's disease. Therefore, the aim of therapeutic research is to target the modification of secretase activity, increase Aβ degradation, reduce Aβ formation, and modulate Aβ-induced neuroinflammation. Recently, the p38 MAP kinase inhibitor CNI-1493 has been shown to reduce plaque load and has led to an improvement in memory performance in a transgenic mouse model. We examined the role of CNI-1493 in the microglial inflammatory response to Aβ using both a microglia cell line as well as primary microglia isolated from mesocortices. MTT assays were performed to quantify cell viability. FACS analysis was used to measure phagocytosis. We used ELISA to analyse cytokine concentrations in response to CNI-1493 treatment. Western-blot/Dot-blot techniques were used to show the interaction of CNI-1493 with Aβ-oligomers as well as to measure apoptosis in microglia cells. RT-PCR was used to analyze secretase expression, and secretase function was determined using fluorimetric assays. CNI-1493 is able to prevent oligomer formation as well as apoptosis in microglia. A significant reduction was found in the Aβ-induced release of IL-6 and TNF-α in the presence of CNI-1493. Phagocytosis is an essential Aβ removal mechanism and was enhanced by CNI-1493 in primary microglia. CNI-1493 also influenced the α-secretase product C83 with an increase in the treated cells, while a simultaneous reduction in Aβ secretion was also observed. We hypothesize that CNI-1493 not only reduces neuroinflammation and consequent neurodegeneration, but also leads to a shift in AβPP-processing towards the non-amyloidogenic pathway. Therefore, CNI-1493 is a promising candidate for the treatment of AD.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs-Aβ) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-Aβ were able to interfere with Aβ peptide toxicity, but NAbs-Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2011; 31(15):5847-54. DOI:10.1523/JNEUROSCI.4401-10.2011 · 6.34 Impact Factor