[Towards more informed consent: Making information understandable].

In clinical research and care, information notices are too often reduced to complicated and hard-to-understand mandatory documents. However, every person has the right to transparent and truthful information. These considerations prompted the creation of a multidisciplinary working group in the fall of 2020, headed by the College des relecteurs de l'Inserm.

Commentary: Global Alzheimer's disease and Alzheimer's disease related dementia research funding organizations support and engage the research community throughout the COVID-19 pandemic.

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates.

Home is where the future is: The BrightFocus Foundation consensus panel on dementia care.

Introduction: A national consensus panel was convened to develop recommendations on future directions for home-based dementia care (HBDC).

Methods: The panel summarized advantages and challenges of shifting to HBDC as the nexus of care and developed consensus-based recommendations.

Results: The panel developed five core recommendations: (1) HBDC should be considered the nexus of new dementia models, from diagnosis to end of life in dementia; (2) new payment models are needed to support HBDC and reward integration of care; (3) a diverse new workforce that spans the care continuum should be prepared urgently; (4) new technologies to promote communication, monitoring/safety, and symptoms management must be tested, integrated, and deployed; and (5) targeted dissemination efforts for HBDC must be employed.

Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome.

The development of 'omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers.

Ceramides and sphingomyelinases in senile plaques.

The senile plaque is a hallmark lesion of Alzheimer disease (AD). We compared, without a priori, the lipidome of the senile plaques and of the adjacent plaque-free neuropil. The analysis by liquid chromatography coupled with electrospray ionization mass spectrometry revealed that laser microdissected senile plaques were enriched in saturated ceramides Cer(d18:1/18:0) and Cer(d18:1/20:0) by 33 and 78% respectively with respect to the surrounding neuropil.

Clearance of genetic variants of amyloid β peptide by neuronal and non-neuronal cells.

The presence of senile plaques in the brain is one of the pathological hallmarks of Alzheimer's disease (AD). The biogenesis and clearance of the amyloid β peptide (A β ), the main component of the lesions, lie at the center of the pathogenesis of AD. In sporadic AD, the increase of A β levels seems to be indicative of failure of clearance mechanisms.

Choline-containing phospholipids in microdissected human Alzheimer's disease brain senile plaque versus neuropil.

Background: Lipidomic studies related to Alzheimer's disease have been reported on either biological fluids or large human brain samples. For a better understanding of the role of lipids, especially during the amyloid-β peptide aggregation, it is crucial to determine the composition of the senile plaque versus the surrounding tissue, that is, the neuropil.

Results: A laser microdissection step was added to the analysis by UPLC-MS/MS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients.

Although cholesterol has been involved in the pathophysiology of Alzheimer disease (AD), its distribution in the cerebral cortex over the course of AD is unknown. We describe an original method to quantify cholesterol distribution using time-of-flight secondary ion mass spectrometry imaging. Cholesterol was unevenly distributed along the cortical thickness, being more abundant close to the white matter, in both control and AD cases.

Decrease of the immunophilin FKBP52 accumulation in human brains of Alzheimer's disease and FTDP-17.

Human neurodegenerative diseases characterized by abnormal intraneuronal inclusions of the tau protein, or "tauopathies", include Alzheimer's disease (AD), Pick's disease, progressive supranuclear palsy, corticobasal degeneration as well as fronto-temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Several abnormalities of tau may contribute to the pathological processes, yet the mechanisms involved in tau cellular toxicity remain unclear. Previously, we demonstrated an interaction between various isoforms of tau and the immunophilin FKBP52 (FK506-Binding Protein), suggesting a direct involvement of FKBP52 in tau function.

Cholesterol changes in Alzheimer's disease: methods of analysis and impact on the formation of enlarged endosomes.

An increasing number of results implicating cholesterol metabolism in the pathophysiology of Alzheimer's disease (AD) suggest cholesterol as a target for treatment. Research in genetics, pathology, epidemiology, biochemistry, and cell biology, as well as in animal models, suggests that cholesterol, its transporter in the brain, apolipoprotein E, amyloid precursor protein, and amyloid-beta all interact in AD pathogenesis. Surprisingly, key questions remain unanswered due to the lack of sensitive and specific methods for assessing cholesterol levels in the brain at subcellular resolution.

Enrichment of cholesterol in microdissected Alzheimer's disease senile plaques as assessed by mass spectrometry.

Extensive knowledge of the protein components of the senile plaques, one of the hallmark lesions of Alzheimer's disease, has been acquired over the years, but their lipid composition remains poorly known. Evidence suggests that cholesterol contributes to the pathogenesis of Alzheimer's disease. However, its presence within senile plaques has never been ascertained with analytic methods.

Cholesterol in the senile plaque: often mentioned, never seen.

The lipid components of the senile plaque (SP) remain largely unknown. Senile plaques were said to be enriched in cholesterol in a few studies using the cholesterol probe filipin and a histoenzymatic method based upon cholesterol oxidase activity. We provide data that strongly suggest that these results are false-positive: the SPs were still stained in the absence of the enzyme cholesterol oxidase; filipin still labeled the plaques after lipid extraction.

Clearance of amyloid-beta peptide by neuronal and non-neuronal cells: proteolytic degradation by secreted and membrane associated proteases.

Deposition of amyloid-beta peptide (Abeta) in the brain is an early and invariant feature of all forms of Alzheimer's disease (AD). As for all proteins or peptides, the steady-state level of Abeta peptide is determined not only by its production, but also by its degradation. So, overactive proteases involved in generating Abeta from amyloid precursor protein or underactive Abeta-degrading enzymes could lead to abnormal Abeta deposition in the brain.

Reactivity of basic amino acid pairs in prohormone processing: model of pro-ocytocin/neurophysin processing domain.

Statistical analysis of several potential dibasic cleavage sites reveals differences in the distribution of basic doublets when the in vivo cleaved sites were compared to those which are not cleaved. Analysis of the substrate specificity of protease Kex2 towards the pro-ocytocin/neurophysin processing domain (pro-OT/Np(7-15) with altered basic pairs shows a cleavage efficiency order in accord with the statistical data. Structural analysis of these substrates indicates that each basic pair is associated with a local and specific conformational change.

Abnormalities of peptide metabolism in Alzheimer disease.

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism.

Specific cleavage of beta-amyloid peptides by a metallopeptidase from Xenopus laevis skin secretions.

Dactylysin (EC 3.5.24.

The somatostatin-28(1-12)-NPAMAP sequence: an essential helical-promoting motif governing prosomatostatin processing at mono- and dibasic sites.

Proline residues, known to have special structural properties, induce particular conformations which participate in some biological functions. Two prolines (Pro(-9), Pro(-5)) located near the processing sites (Arg(-15) and Arg(-2)Lys(-)(1)) of human prosomatostatin were previously shown to be important for cleavage of the precursor into somatostatin-28 (S-28) and somatostatin-14 (S-14) [Gomez et al. (1989) EMBO J.