CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease.

Autosomal dominant Alzheimer's disease (ADAD) offers a unique opportunity to study pathophysiological changes in a relatively young population with few comorbidities. A comprehensive investigation of proteome changes occurring in ADAD could provide valuable insights into AD-related biological mechanisms and uncover novel biomarkers and therapeutic targets. Furthermore, ADAD might serve as a model for sporadic AD, but in-depth proteome comparisons are lacking. We aimed to identify dysregulated CSF proteins in ADAD and determine the degree of overlap with sporadic AD. We measured 1472 proteins in CSF of PSEN1 or APP mutation carriers (n = 22) and age- and sex-matched controls (n = 20) from the Amsterdam Dementia Cohort using proximity extension-based immunoassays (PEA). We compared protein abundance between groups with two-sided t-tests and identified enriched biological pathways. Using the same protein panels in paired plasma samples, we investigated correlations between CSF proteins and their plasma counterparts. Finally, we compared our results with recently published PEA data from an international cohort of sporadic AD (n = 230) and non-AD dementias (n = 301). All statistical analyses were false discovery rate-corrected. We detected 66 differentially abundant CSF proteins (65 increased, 1 decreased) in ADAD compared to controls (q < 0.05). The most strongly upregulated proteins (fold change >1.8) were related to immunity (CHIT1, ITGB2, SMOC2), cytoskeletal structure (MAPT, NEFL) and tissue remodelling (TMSB10, MMP-10). Significant CSF-plasma correlations were found for the upregulated proteins SMOC2 and LILR1B. Of the 66 differentially expressed proteins, 36 had been measured previously in the sporadic dementias cohort, 34 of which (94%) were also significantly upregulated in sporadic AD, with a strong correlation between the fold changes of these proteins in both cohorts (rs = 0.730, P < 0.001). Twenty-nine of the 36 proteins (81%) were also upregulated among non-AD patients with suspected AD co-pathology. This CSF proteomics study demonstrates substantial biochemical similarities between ADAD and sporadic AD, suggesting involvement of the same biological processes. Besides known AD-related proteins, we identified several relatively novel proteins, such as TMSB10, MMP-10 and SMOC2, which have potential as novel biomarkers. With shared pathophysiological CSF changes, ADAD study findings might be translatable to sporadic AD, which could greatly expedite therapy development.

Beyond Tumors: Gastric Syphilis Emulating a Gastric Neoplasia.

We present the case of a 35-year-old male with a first-degree family history of gastric cancer (his father was diagnosed at the age of 45), who was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Neuroinflammatory CSF biomarkers MIF, sTREM1, and sTREM2 show dynamic expression profiles in Alzheimer's disease.

BACKGROUND: There is a need for novel fluid biomarkers tracking neuroinflammatory responses in Alzheimer's disease (AD). Our recent cerebrospinal fluid (CSF) proteomics study revealed that migration inhibitory factor (MIF) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1) increased along the AD continuum. We aimed to assess the potential use of these proteins, in addition to sTREM2, as CSF biomarkers to monitor inflammatory processes in AD. METHODS: We included cognitively unimpaired controls (n = 67, 63 ± 9 years, 24% females, all amyloid negative), patients with mild cognitive impairment (MCI; n = 92, 65 ± 7 years, 47% females, 65% amyloid positive), AD (n = 38, 67 ± 6 years, 8% females, all amyloid positive), and DLB (n = 50, 67 ± 6 years, 5% females, 54% amyloid positive). MIF, sTREM1, and sTREM2 levels were measured by validated immunoassays. Differences in protein levels between groups were tested with analysis of covariance (corrected for age and sex). Spearman correlation analysis was performed to evaluate the association between these neuroinflammatory markers with AD-CSF biomarkers (Aß42, tTau, pTau) and mini-mental state examination (MMSE) scores. RESULTS: MIF levels were increased in MCI (p < 0.01), AD (p < 0.05), and DLB (p > 0.05) compared to controls. Levels of sTREM1 were specifically increased in AD compared to controls (p < 0.01), MCI (p < 0.05), and DLB patients (p > 0.05), while sTREM2 levels were increased specifically in MCI compared to all other groups (all p < 0.001). Neuroinflammatory proteins were highly correlated with CSF pTau levels (MIF: all groups; sTREM1: MCI, AD and DLB; sTREM2: controls, MCI and DLB). Correlations with MMSE scores were observed in specific clinical groups (MIF in controls, sTREM1 in AD, and sTREM2 in DLB). CONCLUSION: Inflammatory-related proteins show diverse expression profiles along different AD stages, with increased protein levels in the MCI stage (MIF and sTREM2) and AD stage (MIF and sTREM1). The associations of these inflammatory markers primarily with CSF pTau levels indicate an intertwined relationship between tau pathology and inflammation. These neuroinflammatory markers might be useful in clinical trials to capture dynamics in inflammatory responses or monitor drug-target engagement of inflammatory modulators.

Hepatosplenic schistosomiasis: an uncommon cause of liver disease in developed countries.

Schistosomiasis is a parasitic infection caused by trematode species of the genus Schistosoma. It is prevalent in tropical regions of Africa, Asia and South America, being rare in Europe, where it is usually diagnosed in immigrants and tourists from endemic areas. It has different clinical forms of presentation. Hepatosplenic schistosomiasis produces periportal fibrosis, which can progress to presinusoidal portal hypertension, with all its associated complications. We present the case of a 43-year-old female patient from the Philippines who was referred to gastroenterology consultation due to liver enzyme alteration with a predominantly cholestatic pattern. An aetiological study was performed, with negative results. An abdominal ultrasound revealed signs of chronic liver disease, with transient elastography of 9.5 kPa. A percutaneous liver biopsy was performed, with histological findings consistent with infestation by schistosome eggs, receiving treatment with praziquantel and subsequently verifying its eradication with a stool test.

Apolipoprotein L1 is increased in frontotemporal lobar degeneration post-mortem brain but not in ante-mortem cerebrospinal fluid.

AIMS: Frontotemporal Dementia (FTD) is caused by frontal-temporal lobar degeneration (FTLD), characterized mainly by brain protein aggregates of tau (FTLD-Tau) or TDP-43 (FTLD-TDP). The clinicopathological heterogeneity makes ante-mortem diagnosis of these pathological subtypes challenging. Our proteomics study showed increased Apolipoprotein L1 (APOL1) levels in CSF from FTD patients, which was prominently expressed in FTLD-Tau. We aimed to understand APOL1 expression in FTLD post-mortem brain tissue and to validate its potential as a CSF biomarker for FTD and its pathological subtypes. METHODS: APOL1 levels were analyzed in the frontal cortex of FTLD (including FTLD-Tau and FTLD-TDP) and non-demented controls by immunohistochemistry (FTLD total = 18 (12 FTLD-Tau and 6 FTLD-TDP); controls = 9), western blot (WB), and a novel prototype ELISA (FTLD total = 44 (21 FTLD-Tau and 23 FTLD-TDP); controls = 9). The association of APOL1 immunoreactivity with phosphorylated Tau (pTau) and TDP-43 (pTDP-43) immunoreactivity was assessed. CSF APOL1 was analyzed in confirmed FTD patients (n = 27, including 12 FTLD-Tau and 15 FTLD-TDP) and controls (n = 15) using the same ELISA. RESULTS: APOL1 levels were significantly increased in FTLD post-mortem tissue compared to controls as measured by immunohistochemistry, WB, and ELISA. However, no differences between the pathological subtypes were observed. APOL1 immunoreactivity was present in neuronal and glial cells but did not co-localize with pTau or pTDP-43. CSF APOL1 levels were comparable between FTD patients and controls and between pathological subtypes. CONCLUSION: APOL1 is upregulated in FTLD pathology irrespective of the subtypes, indicating a role of this novel protein in FTD pathophysiology. The APOL1 levels detected in brain tissue were not mirrored in the CSF, limiting its potential as a specific FTD biofluid-based biomarker using our current immunoassay.

New developments of biofluid-based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia.

Frontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with different phenotypes, genetic backgrounds, and pathological states. Its clinicopathological diversity challenges the diagnostic process and the execution of clinical trials, calling for specific diagnostic biomarkers of pathologic FTD types. There is also a need for biomarkers that facilitate disease staging, quantification of severity, monitoring in clinics and observational studies, and for evaluation of target engagement and treatment response in clinical trials. This review discusses current FTD biofluid-based biomarker knowledge taking into account the differing applications. The limitations, knowledge gaps, and challenges for the development and implementation of such markers are also examined. Strategies to overcome these hurdles are proposed, including the technologies available, patient cohorts, and collaborative research initiatives. Access to robust and reliable biomarkers that define the exact underlying pathophysiological FTD process will meet the needs for specific diagnosis, disease quantitation, clinical monitoring, and treatment development.

Spanish adaptation of the quality in psychiatric care-outpatient (QPC-OP) instrument community mental health patients' version: psychometric properties and factor structure.

BACKGROUND: Health systems in the field of mental health are strongly committed to community models that allow patients to be attended in their own environment. This helps them to maintain their family and social ties while trying to avoid costly hospital admissions. The patients' perspective is a key component in the assessment of the quality of psychiatric care and can even determine their adherence to the devices where they are treated. However, there are few instruments with adequate psychometric properties for the evaluation of the quality of psychiatric care in community mental health. The Quality in Psychiatric Care - Outpatient (QPC-OP) instrument has adequate psychometric properties to assess the quality of psychiatric care from the patients' perspective. The aim of this study was to adapt and validate the Spanish version of the QPC-OP instrument. METHODS: A translation and back-translation of the instrument was carried out. To examine its psychometric properties, the instrument was administered to 200 patients attending various community mental health services. To assess test-retest reliability, the instrument was readministered after 7-14 days (n = 98). RESULTS: The Confirmatory Factor Analysis revealed a structure of 8 factors identical to the original version, with an adequate model fit. The internal consistency coefficient (Cronbach's alpha) was 0.951. The intraclass correlation coefficient was 0.764 (95% IC: 0.649 - 0.842), and higher than 0.70 in 5 of the 8 factors. Additionally, an EFA was performed and revealed that the instrument could behave in a unifactorial or four factor manner in the sample analyzed. CONCLUSIONS: Results show that the Spanish version of the QPC-OP instrument is valid and reliable for the assessment of quality of psychiatric care in the community setting.

Role of Receptor Protein Tyrosine Phosphatase ß/ζ in Neuron-Microglia Communication in a Cellular Model of Parkinson's Disease.

Pleiotrophin (PTN) is a neurotrophic factor that regulates glial responses in animal models of different types of central nervous system (CNS) injuries. PTN is upregulated in the brain in different pathologies characterized by exacerbated neuroinflammation, including Parkinson's disease. PTN is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) ß/ζ, which is abundantly expressed in the CNS. Using a specific inhibitor of RPTPß/ζ (MY10), we aimed to assess whether the PTN/RPTPß/ζ axis is involved in neuronal and glial injury induced by the toxin MPP+. Treatment with the RPTPß/ζ inhibitor MY10 alone decreased the viability of both SH-SY5Y neuroblastoma cells and BV2 microglial cultures, suggesting that normal RPTPß/ζ function is involved in neuronal and microglial viability. We observed that PTN partially decreased the cytotoxicity induced by MPP+ in SH-SY5Y cells underpinning the neuroprotective function of PTN. However, MY10 did not seem to modulate the SH-SY5Y cell loss induced by MPP+. Interestingly, we observed that media from SH-SY5Y cells treated with MPP+ and MY10 decreases microglial viability but may elicit a neuroprotective response of microglia by upregulating Ptn expression. The data suggest a neurotrophic role of microglia in response to neuronal injury through upregulation of Ptn levels.

A Spanish adaptation of the Quality in Psychiatric Care-Inpatient (QPC-IP) instrument: Psychometric properties and factor structure.

BACKGROUND AND AIM: Western countries share an interest in evaluating and improving quality of care in the healthcare field. The aim was to develop and examine the psychometric properties and factor structure of the Spanish version of the Quality in Psychiatric Care-Inpatient (QPC-IP) instrument. METHODS: A psychometric study was conducted, translating the QPC-IPS instrument into Spanish, revision of the instrument by a panel of experts, and assessing its psychometric properties. 150 psychiatric inpatients completed the QPC-IP. Test-retest reliability was assessed by re-administering the questionnaire to 75 of these patients. RESULTS: After conducting pilot testing and a cognitive interview with 30 inpatients, it was determined that the QPC-IPS was adequate and could be self-administered. A Cronbach's alpha of 0.94 was obtained for the full instrument and values of 0.52-0.89 for the various dimensions of the questionnaire. Test re test reliability: The Intraclass Correlation Coefficient for the full questionnaire was 0.69, while for the individual dimensions values between 0.62 and 0.74 were obtained, indicating acceptable temporal stability. Convergent validity was analysed using 10-point numerical satisfaction scale, giving a positive correlation (0.49). Confirmatory factor analysis revealed six factors consistent with the original scale. The Spanish version yielded adequate results in terms of validity and reliability. CONCLUSION: Our findings provide evidence of the convergent validity, reliability, temporal stability and construct validity of the Spanish QPC-IP for measuring patient quality in psychiatric care in Spanish hospitals. Hospital administrators can use this tool to assess and identify areas for improvement to enhance quality in psychiatric care.

Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia.

BACKGROUND: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. METHODS: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). RESULTS: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. CONCLUSION: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.

Dietary plant phenolic improves survival of bacterial infection in Manduca sexta caterpillars.

Plant phenolics are generally thought to play significant roles in plant defense against herbivores and pathogens. Many plant taxa, including Solanaceae, are rich in phenolic compounds and some insect herbivores have been shown to acquire phenolics from their hosts to use them as protection against their natural enemies. Here we demonstrate that larvae of an insect specialist on Solanaceae, the tobacco hornworm, Manduca sexta L. (Lepidoptera: Sphingidae), acquire the plant phenolic chlorogenic acid (CA), and other caffeic acid derivatives as they feed on one of their hosts, Nicotiana attenuata L. (Solanaceae), and on artificial diet supplemented with CA. We test the hypothesis that larvae fed on CA-supplemented diet would have better resistance against bacterial infection than larvae fed on a standard CA-free diet by injecting bacteria into the hemocoel of fourth instars. Larvae fed CA-supplemented diet show significantly higher survival of infection with Enterococcus faecalis (Andrewes & Horder) Schleifer & Kilpper-Bälz, but not of infection with the more virulent Pseudomonas aeruginosa (Schroeter) Migula. Larvae fed on CA-supplemented diet possess a constitutively higher number of circulating hemocytes than larvae fed on the standard diet, but we found no other evidence of increased immune system activity, nor were larvae fed on CA-supplemented diet better able to suppress bacterial proliferation early in the infection. Thus, our data suggest an additional defensive function of CA to the direct toxic inhibition of pathogen proliferation in the gut.

Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross-platform validation study.

INTRODUCTION: Our previous antibody-based cerebrospinal fluid (CSF) proteomics study showed that Thimet oligopeptidase (THOP1), an amyloid beta (Aß) neuropeptidase, was increased in mild cognitive impairment with amyloid pathology (MCI-Aß+) and Alzheimer's disease (AD) dementia compared with controls and dementia with Lewy bodies (DLB), highlighting the potential of CSF THOP1 as an early specific biomarker for AD. We aimed to develop THOP1 immunoassays for large-scale analysis and validate our proteomics findings in two independent cohorts. METHODS: We developed in-house CSF THOP1 immunoassays on automated Ella and Simoa platforms. The performance of the different assays were compared using Passing-Bablok regression analysis in a subset of CSF samples from the discovery cohort (n = 72). Clinical validation was performed in two independent cohorts (cohort 1: n = 200; cohort 2: n = 165) using the Ella platform. RESULTS: THOP1 concentrations moderately correlated between proteomics analysis and our novel assays (Rho > 0.580). In both validation cohorts, CSF THOP1 was increased in MCI-Aß+ (>1.3-fold) and AD (>1.2-fold) compared with controls; and between MCI-Aß+ and DLB (>1.2-fold). Higher THOP1 concentrations were detected in AD compared with DLB only when both cohorts were analyzed together. In both cohorts, THOP1 correlated with CSF total tau (t-tau), phosphorylated tau (p-tau), and Aß40 (Rho > 0.540) but not Aß42. DISCUSSION: Validation of our proteomics findings underpins the potential of CSF THOP1 as an early specific biomarker associated with AD pathology. The use of antibody-based platforms in both the discovery and validation phases facilitated the translation of proteomics findings, providing an additional workflow that may accelerate the development of biofluid-based biomarkers.

Quality in Psychiatric Care in the Community Mental Health Setting from the Perspective of Patients and Staff.

The current paradigm of mental health care focuses on care provided in the community, increasingly moving away from hospital care models that involve considerable economic burden. Patient and staff perspectives on the quality of psychiatric care can highlight strengths and areas for improvement to ensure better care provision. The aim of this study was to describe and compare perceptions of quality of care among patients and staff in community mental health services and to determine possible relationships between these perceptions and other study variables. A comparative cross-sectional descriptive study was conducted in a sample of 200 patients and 260 staff from community psychiatric care services in the area of Barcelona (Spain). The results showed high overall levels of quality of care from patient (m = 104.35 ± 13.57) and staff (m =102.06 ± 8.80) perspectives. Patients and staff both gave high scores to Encounter and Support factors, while factors concerning patient Participation and Environment received the lowest scores. Continuous assessment of the quality of psychiatric care in the community setting is essential to ensure the highest quality of care, taking the perspectives of those involved into account.

Discovery of novel CSF biomarkers to predict progression in dementia using machine learning.

Providing an accurate prognosis for individual dementia patients remains a challenge since they greatly differ in rates of cognitive decline. In this study, we used machine learning techniques with the aim to identify cerebrospinal fluid (CSF) biomarkers that predict the rate of cognitive decline within dementia patients. First, longitudinal mini-mental state examination scores (MMSE) of 210 dementia patients were used to create fast and slow progression groups. Second, we trained random forest classifiers on CSF proteomic profiles and obtained a well-performing prediction model for the progression group (ROC-AUC = 0.82). As a third step, Shapley values and Gini feature importance measures were used to interpret the model performance and identify top biomarker candidates for predicting the rate of cognitive decline. Finally, we explored the potential for each of the 20 top candidates in internal sensitivity analyses. TNFRSF4 and TGF [Formula: see text]-1 emerged as the top markers, being lower in fast-progressing patients compared to slow-progressing patients. Proteins of which a low concentration was associated with fast progression were enriched for cell signalling and immune response pathways. None of our top markers stood out as strong individual predictors of subsequent cognitive decline. This could be explained by small effect sizes per protein and biological heterogeneity among dementia patients. Taken together, this study presents a novel progression biomarker identification framework and protein leads for personalised prediction of cognitive decline in dementia.

CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease.

Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. We employed proximity extension-based assays to measure 665 proteins in the cerebrospinal fluid (CSF) from patients with DLB (n = 109), Alzheimer´s disease (AD, n = 235) and cognitively unimpaired controls (n = 190). We identified over 50 CSF proteins dysregulated in DLB, enriched in myelination processes among others. The dopamine biosynthesis enzyme DDC was the strongest dysregulated protein, and could efficiently discriminate DLB from controls and AD (AUC:0.91 and 0.81 respectively). Classification modeling unveiled a 7-CSF biomarker panel that better discriminate DLB from AD (AUC:0.93). A custom multiplex panel for six of these markers (DDC, CRH, MMP-3, ABL1, MMP-10, THOP1) was developed and validated in independent cohorts, including an AD and DLB autopsy cohort. This DLB CSF proteome study identifies DLB-specific protein changes and translates these findings to a practicable biomarker panel that accurately identifies DLB patients, providing promising diagnostic and clinical trial testing opportunities.

Adaptation, psychometric properties and factor structure of the Spanish Quality in Psychiatric Care-Outpatient Staff (QPC-OPS) instrument.

Quality of care is a multidimensional concept that should include the perspectives of all parties involved. There are few instruments with adequate psychometric properties for the assessment of the quality of psychiatric care in community mental health. Quality in Psychiatric Care-Outpatient Staff (QPC-OPS) instrument has adequate psychometric properties to evaluate the quality of psychiatric care from the perspective of professionals. The aim of this study was to validate the Spanish version of the QPC-OPS instrument. The instrument was translated and back-translated, and then was administered to 260 professionals from distinct community mental health services. To assess test-retest reliability, it was re-administered after 7-14 days (n = 157). Confirmatory factor analysis revealed an 8-factor-structure identical to the original version, showing the good fit of the model. The internal consistency coefficient (Cronbach's alpha) was 0.885. The intraclass correlation coefficient was 0.847 (95% IC 0.790-0.888), which was higher than 0.70 in all factors bar one. The NT394 General Satisfaction Scale was used for analysis of convergent validity showing a rho correlation of 0.31 (p < 0.0001). Results show that the Spanish version of the QPC-OPS instrument is valid and reliable for the assessment of the quality of psychiatric care in the community setting.

YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer's disease and frontotemporal lobar degeneration.

BACKGROUND: YKL-40 (Chitinase 3-like I) is increased in CSF of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) patients and is therefore considered a potential neuroinflammatory biomarker. Whether changed YKL-40 levels in the CSF reflect dysregulation of YKL-40 in the brain is not completely understood yet. We aimed to extensively analyze YKL-40 levels in the brain of AD and different FTLD pathological subtypes. The direct relationship between YKL-40 levels in post-mortem brain and ante-mortem CSF was examined in a small set of paired brain-CSF samples. METHOD: YKL-40 was analyzed in post-mortem temporal and frontal cortex of non-demented controls and patients with AD and FTLD (including FTLD-Tau and FTLD-TDP) pathology by immunohistochemistry (temporal cortex: 51 controls and 56 AD and frontal cortex: 7 controls and 24 FTLD patients), western blot (frontal cortex: 14 controls, 5 AD and 67 FTLD patients), or ELISA (temporal cortex: 11 controls and 7 AD and frontal cortex: 14 controls, 5 AD and 67 FTLD patients). YKL-40 levels were also measured in paired post-mortem brain and ante-mortem CSF samples from dementia patients (n = 9, time-interval collection: 1.4 years) by ELISA. RESULTS: We observed that YKL-40 post-mortem brain levels were similar between AD, FTLD, and controls as shown by immunohistochemistry, western blot, and ELISA. Interestingly, strong YKL-40 immunoreactivity was observed in AD cases with cerebral amyloid angiopathy (CAA; n = 6). In paired CSF-brain samples, YKL-40 concentration was 8-times higher in CSF compared to brain. CONCLUSION: Our data suggest that CSF YKL-40 changes may not reflect YKL-40 changes within AD and FTLD pathological brain areas. The YKL-40 reactivity associated with classical CAA hallmarks indicates a possible relationship between YKL-40, neuroinflammation, and vascular pathology.

Blood-based biomarkers for Alzheimer's disease: towards clinical implementation.

For many years, blood-based biomarkers for Alzheimer's disease seemed unattainable, but recent results have shown that they could become a reality. Convincing data generated with new high-sensitivity assays have emerged with remarkable consistency across different cohorts, but also independent of the precise analytical method used. Concentrations in blood of amyloid and phosphorylated tau proteins associate with the corresponding concentrations in CSF and with amyloid-PET or tau-PET scans. Moreover, other blood-based biomarkers of neurodegeneration, such as neurofilament light chain and glial fibrillary acidic protein, appear to provide information on disease progression and potential for monitoring treatment effects. Now the question emerges of when and how we can bring these biomarkers to clinical practice. This step would pave the way for blood-based biomarkers to support the diagnosis of, and development of treatments for, Alzheimer's disease and other dementias.

Cross-cultural adaptation and psychometric properties of the Spanish Quality in Psychiatric Care Forensic Inpatient Staff (QPC-FIPS) instrument.

"Quality in Psychiatric Care-Forensic Inpatient Staff (QPC-FIPS) is an instrument of Swedish origin validated to measure the perception of the quality of mental health care provided by forensic psychiatry professionals. The aim of this study was to cross-culturally adapt the QPC-FIPS instrument and to evaluate the psychometric properties of the Spanish version of the instrument. A psychometric study was carried out. For validity, content validity, convergent validity and construct validity were included. For reliability, the analysis of internal consistency and temporal stability was included. The sample consisted of 153 mental health professionals from four Forensic Psychiatry units. The adapted Spanish version of the QPC-FIPS scale was configured with the same number of items and dimensions as the original. The psychometric properties, in terms of temporal stability and internal consistency, were adequate and the factor structure, such as the homogeneity of the dimensions of the Spanish version of the QPC-FIPS, was equivalent to the original Swedish version. We found that the QPC_FIPS-Spanish is a valid, reliable and easy-to-apply instrument for assessing the self-perception of professionals regarding the care they provide.