Cerebrospinal Fluid Tau, p-Tau 181 and Amyloid-beta(38/40/42) in Frontotemporal Dementias and Primary Progressive Aphasias

Background/Aims: We determined cerebrospinal fluid (CSF) concentrations of amyloid-beta(A beta)(1-38), A beta(1-40), A beta(1-42), total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer's dementia (AD, n = 25) and nondemented controls (n = 20). Methods: Commercially available ELISA and electrochemiluminescence methods were applied. Results: High CSF p-tau and low ratios of A beta(1-42)/A beta(1-40) and A beta(1-42)/A beta(1-38), respectively, were specific for AD. CSF A beta(1-38) was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD. Conclusion: This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations. Copyright (C) 2010 S. Karger AG, Base

Nonsteroidal Anti-Inflammatory Drugs and Ectodomain Shedding of the Amyloid Precursor Protein

Background: Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). Several mechanisms have been proposed to explain these findings including increased shedding of the soluble ectodomain of the amyloid precursor protein (sAPP), which functions as a neurotrophic and neuroprotective factor in vitro and in vivo. Objective: To clarify whether NSAIDs consistently stimulate sAPP secretion. Methods: 293-EBNA cells with stable overexpression of an APP-alkaline phosphatase fusion protein (APP-AP), SH-SY5Y and PC12 cells or primary telencephalic chicken neurons were treated with ibuprofen or indomethacin. APP shedding was then determined by measuring AP activity in conditioned media, Western blot analysis with antibodies against total sAPP or specific for sAPP-alpha, or in a pulse-chase paradigm. Results: AP activity in conditioned media was not increased after NSAID treatment of 293-EBNA cells whereas it was elevated by phorbol ester. Surprisingly, ibuprofen or indomethacin treatment of SH-SY5Y and PC12 cells expressing endogenous APP did not cause changes in sAPP or sAPP-alpha secretion or downregulation of cellular APP. These findings were further corroborated in primary chicken neuronal cultures. Conclusions: Using various experimental settings, we were unable to confirm sAPP or sAPP-alpha stimulation with the NSAIDs ibuprofen and indomethacin in transfected and nontransfected cells of neuronal and nonneuronal origin. Importantly, these findings seem to rule out chronic sAPP stimulation as an alternative mechanism of NSAID action in AD. Copyright (C) 2008 S. Karger AG, Base

Assessing Nigrostriatal Dopaminergic Pathways via 123I-FP-CIT SPECT in Dementia With Lewy Bodies in a Psychiatric Patient Cohort

Background(123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortro- pane single photon emission computed tomography (123I-FP-CIT SPECT) was validated to distinguish Alzheimer’s dementia from dementia with Lewy Bodies (DLB) by European medical agencies. Little evidence exists that validates 123 I-FP-CIT SPECT as a supplementary method to diagnose probable DLB in a psychiatric cohort of patients with psychiatric symptomatology and suspected DLB. We aim to elucidate differences in the clinical phenotype of DLB between those patients with and those without a positive 123 I-FP-CIT SPECT indicating a nigrostriatal deficit.MethodsTo investigate this, we included 67 patients from the Department of Psychiatry and Psychotherapy at University Medical Center Göttingen (UMG) in our study who had undergone 123I-FP-CIT SPECT in the Department of Nuclear Medicine (UMG) by evaluating their patient files.Results55% with a positive-123I-FP-CIT SPECT and probable DLB after the 123I-FP-CIT SPECT exhibited psychiatric features. The number of probable DLB patients in those exhibiting psychiatric symptoms was higher post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT assessed cross-sectionally over a 6-year period (p < 0.05). In addition, prodromal DLB and prodromal DLB patients with a psychiatric-phenotype yielded higher numbers post-123I-FP-CIT SPECT than pre-123I-FP-CIT SPECT (p < 0.05). Furthermore, we discovered no phenotypical differences between those DLB patients with a positive and those with a negative 123I-FP-CIT SPECT. 123I-FP-CIT SPECT-positive DLB patients in our psychiatric cohort revealed a psychiatric onset more often (52%); DLB was less often characterized by an MCI onset (26%) (p < 0.005).ConclusionsOur findings support 123I-FP-CIT SPECT as an adjuvant tool for improving the diagnosis of probable DLB and prodromal DLB in a cohort of psychiatric patients with often concomitant psychiatric symptomatology. The psychiatric-onset is more frequent than an MCI-onset in DLB patients presenting nigrostriatal dysfunction, giving us an indication of the relevance of deep clinical phenotyping in memory clinics that includes the assessment of psychopathology

Mesenchymal Stem Cells for Optimizing Bone Volume at the Dental Implant Recipient Site

Inadequate bone volume at the implant recipient site presents a clinical challenge for many dental practitioners. To overcome these problems, several approaches have been developed and are currently used, including bone grafting strategies and distraction osteogenesis. Mesenchymal stem cells (MSCs) have gained their popularity within the last two decades, with regard to promising clinical results in improving the bone architecture at the implant recipient site. The aim of this chapter was to briefly outline the accessibility properties, differentiation capacities, isolation, and characterization of MSCs with regard to optimizing bone volume in dental implantology. Additionally, potential benefits and pitfalls are discussed in comparison with the conventional bone augmentation techniques

Creutzfeldt-Jakob disease and homocysteine levels in plasma and cerebrospinal fluid

Background: There is evidence that homocysteine contributes to various neurodegenerative disorders. Objective: To assess the values of homocysteine in patients with Creutzfeldt-Jakob disease (CJD) in both cerebrospinal fluid (CSF) and plasma. Methods: Study design: Case control study. Total homocysteine was quantified in CSF and plasma samples of CJD patients (n = 13) and healthy controls (n = 13). Results: Mean values in healthy controls: 0.15 mumol/l +/- 0.07 (CSF) and 9.10 mumol/l +/- 2.99 (plasma); mean values in CJD patients: 0.13 mumol/l +/- 0.03 (CSF) and 9.22 mumol/l +/- 1.81 (plasma). No significant differences between CJD patients and controls were observed (Mann-Whitney U, p > 0.05). Conclusions: The results indicate that the CSF and plasma of CJD patients showed no higher endogenous levels of homocysteine as compared to normal healthy controls. These findings provide no evidence for an additional role of homocysteine in the pathogenetic mechanisms underlying CJD neurodegeneration. Copyright (C) 2005 S. Karger AG, Basel

Systematic review on diabetes mellitus and dental implants: an update

Purpose Dental implant surgery was developed to be the most suitable and comfortable instrument for dental and oral rehabilitation in the past decades, but with increasing numbers of inserted implants, complications are becoming more common. Methods A systematic literature research based on the PRISMA statement was conducted to answer the PICO question "Do diabetic patients with dental implants have a higher complication rate in comparison to healthy controls?". We included 40 clinical studies and 16 publications of aggregated literature in this systematic review. Results We conclude that patients with poorly controlled diabetes mellitus suffer more often from peri-implantitis, especially in the post-implantation time. Moreover, these patients show higher implant loss rates than healthy individuals in long term. Whereas, under controlled conditions success rates are similar. Perioperative anti-infective therapy, such as the supportive administration of antibiotics and chlorhexidine, is the standard nowadays as it seems to improve implant success. Only few studies regarding dental implants in patients with prediabetic conditions are available, indicating a possible negative effect on developing peri-implant diseases but no influence on implant survival. Conclusion Dental implant procedures represent a safe way of oral rehabilitation in patients with prediabetes or diabetes mellitus, as long as appropriate precautions can be adhered to. Accordingly, under controlled conditions there is still no contraindication for dental implant surgery in patients with diabetes mellitus or prediabetic conditions

Analytical performance and clinical utility of the INNOTEST (R) PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Background: Total tau (T-tau) and beta-amyloid((1-42)) (A beta(1-42)) levels in cerebrospinal fluid (CSF) can differentiate Alzheimer's disease (AD) from normal aging or depressive pseudo-dementia. Differential diagnosis from dementia with Lewy bodies (DLB) in clinical settings is difficult. Methods: The analytical performance of the INNOTEST (R) PHOSPHO-TAU((181P)) assay was validated in terms of selectivity, sensitivity, specificity, precision, robustness, and stability. Clinical utility of the assay alone, or combined with T-tau and AP1-421 for discrimination of AD (n=94) from patients suffering from DLB (n=60) or from age-matched control subjects (CS) (n=60) was assessed in a multicenter study. Results: CSF concentrations of tau phosphorylated at threonine 181 (P-tau(181P)) in AD was significantly higher than in DLB and CS. Discriminant analysis, a classification tree, and logistic regression showed that P-tau(181P) was the most statistically significant single variable of the three biomarkers for discrimination between AD and DLB. Conclusions: P-tau(181P) quantification is a robust and reliable assay that may be useful in discriminating AD from DLB