Planning for Institutional Development and Developing Budgets and Financial Management Systems

This section lays out issues related to strategic planning by the Foundation for Community Development (FDC) and illustrates the development of budgets and financial management systems by the Philippine Business for Social Progress (PBSP). Also explored here is the financial reporting system set up by the Esquel Ecuador Foundation (FEE) for their grantees

Cerebrospinal Fluid Biomarkers and Prediction of Conversion in Patients with Mild Cognitive Impairment: 4-Year Follow-Up in a Routine Clinical Setting

Mild cognitive impairment (MCI) is a very common syndrome in elderly people, with a high risk of conversion to dementia. Several investigations have shown the usefulness of cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau [T-tau], and phosphorylated tau [P-tau]) in predicting the progression to Alzheimer's disease (AD). We report a 4-year follow-up of MCI patients who underwent CSF evaluation for biomarker assessment, in order to further evaluate the usefulness of CSF analysis in predicting the conversion to dementia in a routine clinical setting. We identified 55 patients with MCI among the consecutive patients, referred from 2001 to 2003 to our Memory Clinic for cognitive disorders, who underwent a complete diagnostic assessment, including lumbar puncture (n = 273). At the end of the follow-up, 31 MCI patients (56%) did not progress to dementia (stable MCI), while 24 (44%) developed a dementia condition. At baseline, the mean levels of CSF Aβ42, T-tau, and P-tau were significantly altered in MCI patients who were converting to dementia with respect to those with stable MCI. All MCI patients with the three altered CSF biomarkers developed dementia within 1 year. Among the stable MCI patients, none showed all three pathological values and only one subject had the pathological value of P-tau. Early diagnosis of dementia and, specifically, a correct prediction of MCI outcome represent a primary goal. To this respect, the role of CSF biomarkers seems to be crucial in a routine clinical setting

role of fabp3 as biomarker in alzheimer s disease and synucleinopathies

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Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease

Background: Decreased concentrations of amyloid-β 1-42 (Aβ(42)) in cerebrospinal fluid (CSF) and increased retention of Aβ tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer’s disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism. The CSF Aβ(42/40) ratio seems to be a more accurate biomarker of clinical AD than CSF Aβ(42) alone. Objective: We tested whether CSF Aβ(42) alone or the Aβ(42/40) ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results. Methods: CSF obtained from a mixed cohort (n = 200) of cognitively normal and abnormal research participants who had undergone amyloid PET within 12 months (n = 150 PET-negative, n = 50 PET-positive according to a previously published cut-off) was assayed for Aβ(42) and Aβ(40) using two recently developed immunoassays. Optimal CSF cut-offs for amyloid positivity were calculated, and concordance was tested by comparison of the areas under receiver operating characteristic (ROC) curves (AUC) and McNemar’s test for paired proportions. Results: CSF Aβ(42/40) corresponded better than Aβ(42) with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p < 0.0001) and a larger AUC (0.936 versus 0.814, respectively, p < 0.0001) associated with the ratio. For both CSF biomarkers, the percentage of CSF-abnormal/PET-normal cases was larger than that of CSF-normal/PET-abnormal cases. Conclusion: The CSF Aβ(42/40) ratio is superior to Aβ(42) alone as a marker of amyloid-positivity by PET. We hypothesize that this increase in performance reflects the ratio compensating for general between-individual variations in CSF total Aβ

Value of cerebrospinal fluid α-synuclein species as biomarker in Parkinson's diagnosis and prognosis.

Since diagnosis of Parkinson's disease (PD) is mostly based on clinical criteria, it is almost impossible to formulate an early diagnosis, as well as a timely differential diagnosis versus other parkinsonisms. A great effort in searching reliable biomarkers both for early diagnosis and prognosis in PD is currently ongoing. Cerebrospinal fluid has been widely investigated as potential source for such biomarkers, with particular emphasis on α-synuclein (α-syn) species. We reviewed all the clinical studies carried out so far on cerebrospinal fluid quantification of α-syn species in PD. Current evidence supports the value of total and oligomeric α-syn in PD diagnosis and in the differential diagnosis of PD and other parkinsonisms. Conversely, the role of α-syn species in PD prognosis remains unsatisfactory

Hot water epilepsy and Mccune–Albright syndrome: A case report

AbstractWe observed a 15-year-old Caucasian boy with a rare form of reflex epilepsy, known as hot water epilepsy (HWE), associated to McCune–Albright syndrome (MAS). This is a rare disease due to post-zygotic and somatic mutations of the Gs-alpha gene, that results in cellular mosaicism. Predominant features of MAS occur in the bony skeleton, the skin, the endocrine system, and, in atypical presentations, in other non-endocrine tissues. It is unknown whether or not an expression of the GNAS1 product in the brain does exist. Although the association of MAS with HWE in our patient may be merely casual, it brings up the possibility that the striking phenotypic variability of MAS might also include epilepsy

Welcome to the new open access NeuroSci

With sincere satisfaction and pride, I present to you the new journal, NeuroSci, for which I am pleased to serve as editor-in-chief. To date, the world of neurology has been rapidly advancing, NeuroSci is a cross-disciplinary, open-access journal that offers an opportunity for presentation of novel data in the field of neurology and covers a broad spectrum of areas including neuroanatomy, neurophysiology, neuropharmacology, clinical research and clinical trials, molecular and cellular neuroscience, neuropsychology, cognitive and behavioral neuroscience, and computational neuroscience. Members of our editorial board will welcome the contributions in this wide field of neurosciences. The following are welcome messages from some editorial board members

Pathogenetic mechanisms in vascular dementia

Vascular dementia accounts for approximately 20% of all cases of dementia and for about 50% in subjects over 80 years. Thromboembolism with multiple cerebral infarcts was considered to be almost the only pathogenetic pathway of vascular dementia, with multi-infarct dementia as its clinical manifestation. However, there is a great heterogeneity of vascular dementia syndromes and pathological subtypes, as documented by the number of pathogenetic mechanisms now known to underlie the clinical picture. They include thromboembolism and extracerebral and cerebral factors. Among the extracerebral factors are ischemic hypoxic dementia (i.e., dementia due to hypoperfusion), vasculitis, hyperviscosity and abnormalities of hemostasis. Among the cerebral factors are lipohyalinosis, cerebral amyloid angiopathy, disruption of the blood-brain barrier and altered regulation of cerebral blood flow. Therefore, the approach to vascular dementia should take the heterogeneity into account. In this context, the importance of non-infarct type should be considered; subcortical white matter disorder seems to be a noteworthy common pathway of vascular dementia produced by various vascular mechanisms. Finally, the heterogeneity of the vascular mechanisms involved in vascular dementia-namely hypoperfusion-might be a factor that can be positively influenced by targeted therapeutic intervention

Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer's and Parkinson's disease

BACKGROUND: Increasing evidence implicates dysfunctional proteostasis and the involvement of the autophagic and endo-lysosomal system and the ubiquitin-proteasome system in neurodegenerative diseases. In Alzheimer's disease (AD), there is an accumulation of autophagic vacuoles within the neurons. In Parkinson's disease (PD), susceptibility has been linked to genes encoding proteins involved in autophagy and lysosomal function, as well as mutations causing lysosomal disorders. Furthermore, both diseases are characterized by the accumulation of protein aggregates. METHODS: Proteins associated with endocytosis, lysosomal function, and the ubiquitin-proteasome system were identified in the cerebrospinal fluid (CSF) and targeted by combining solid-phase extraction and parallel reaction monitoring mass spectrometry. In total, 50 peptides from 18 proteins were quantified in three cross-sectional cohorts including AD (N = 61), PD (N = 21), prodromal AD (N = 10), stable mild cognitive impairment (N = 15), and controls (N = 68). RESULTS: A pilot study, including subjects selected based on their AD CSF core biomarker concentrations, showed increased concentrations of several targeted proteins in subjects with core biomarker levels indicating AD pathology compared to controls. Next, in a clinically characterized cohort, lower concentrations in CSF of proteins in PD were found compared to subjects with prodromal AD. Further investigation in an additional clinical study again revealed lower concentrations in CSF of proteins in PD compared to controls and AD. CONCLUSION: In summary, significantly different peptide CSF concentrations were identified from proteins AP2B1, C9, CTSB, CTSF, GM2A, LAMP1, LAMP2, TCN2, and ubiquitin. Proteins found to have altered concentrations in more than one study were AP2B1, CTSB, CTSF, GM2A, LAMP2, and ubiquitin. Interestingly, given the genetic implication of lysosomal function in PD, we did identify the CSF concentrations of CTSB, CTSF, GM2A, and LAMP2 to be altered. However, we also found differences in proteins associated with endocytosis (AP2B1) and the ubiquitin-proteasome system (ubiquitin). No difference in any peptide CSF concentration was found in clinically characterized subjects with AD compared to controls. In conclusion, CSF analyses of subjects with PD suggest a general lysosomal dysfunction, which resonates well with recent genetic findings, while such changes are minor or absent in AD