Alzheimer's Imaging Consortium.

Background: Recent studies highlight distinct patterns of cortical atrophy between amnestic (typical) and non-amnestic (atypical, with subtypes: behavioural, dysexecutive, logopenic and visuospatial) clinical phenotypes of Alzheimer's disease (AD). The current study aimed to assess regional MRI patterns of cortical atrophy across AD phenotypes, and their association with amyloid-beta (Aß), phosphorylated tau (pTau), axonal degeneration (NfL) and microvascular deterioration (COLIV).

Method: Postmortem In-situ 3DT1 3T-MRI data was collected for 33 AD (17 typical, 16 atypical) and 16 control brain donors.

Alzheimer's Imaging Consortium.

Background: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non-demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e.

Alzheimer's Imaging Consortium.

Background: Despite evidence that sex can modulate Alzheimer's disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men.

Method: We included 135 cognitively unimpaired older adults ( = 65 years old, 83 women; Table 1) from the Age-Well trial (NCT02977819; baseline data) with multidomain assessments of modifiable risk factors, including cardiovascular (body mass index, systolic blood pressure, LDL cholesterol), lifestyle (complex mental activity throughout life, physical activity, diet), and psychological (quality of life, depressive and anxiety symptoms, rumination, worry).

Alzheimer's Imaging Consortium.

Background: Brain MRI segmentation is required for quantitative PET analysis, in order to derive regional uptake and calculate uptake ratio relative to reference regions. FreeSurfer has been a popular method but is being supplanted by faster and more robust AI-driven methods. The objective of this work is to confirm that the use of Clario's novel AI segmentation method, whose impact was assessed towards various MRI endpoints, is also valid in the context of PET quantification.

Gonadal function and pathology in 17beta-HSD 3 and 5alpha-reductase deficiency.

Objective: 17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 deficiency (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function and gonadal pathology in these conditions.

Design: Retrospective multicentre cohort study.

Alzheimer's Imaging Consortium.

Background: The heterogeneity of Alzheimer's disease (AD) and lack of well-validated markers of co-pathologies present a substantial challenge for therapeutics. We previously found phenotypes defined by Tau (T) - Neurodegeneration (N) discordance linked to non-Alzheimer's pathologies (e.g.

Alzheimer's Imaging Consortium.

Background: Individuals with Down Syndrome (DS) almost invariably develop Alzheimer's Disease (AD), but detecting early clinical changes is challenging due to comorbid intellectual disability, highlighting the importance of non-invasive biomarkers. Neuroimaging of the medial temporal lobe (MTL), a key site of tau pathology, shows promise as an early AD biomarker. Here, we aimed to characterise volumetric patterns of the MTL in DS across the AD clinical continuum, and define associations with AD cerebrospinal fluid (CSF) biomarkers.

Rotational Excitation Cross Sections for Chloronium Based on a New 5D Interaction Potential with Molecular Hydrogen.

Chloronium (HCl) is an important intermediate of Cl-chemistry in space. The accurate knowledge of its collisional properties allows a better interpretation of the corresponding observations in interstellar clouds and, therefore, a better estimation of its abundance in these environments. While the ro-vibrational spectroscopy of HCl is well-known, the studies of its collisional excitation are rather limited and these are available for the interaction with helium atoms only.

Alzheimer's Imaging Consortium.

Background: The medial temporal lobe's (MTL) early involvement in tau pathology makes it a key focus in the development of preclinical Alzheimer's disease (AD) biomarkers. ROI analyses in prior studies reported significant MTL structural differences in cognitively normal individuals with and without ß-amyloid (A+/-CN). Pointwise analysis, offering spatial information of early neurodegeneration, has potential to pinpoint "signature regions" of pathological change, but has been underexplored in the MTL.

Alzheimer's Imaging Consortium.

Background: Education has been associated with reserve mechanisms and lower dementia risk, but the literature shows inconsistent results on the association between education and brain outcomes across the lifespan. Considering that both dementia risk and education are likely to differ between sexes, our study aims at understanding the association between education and brain outcomes across the lifespan and whether it differs by sex.

Method: In 207 healthy individuals (110women) aged 19-84 years old (47.

Comprehensive exploration of unexplained dyspnoea in subjects with normal ejection fraction and low natriuretic peptides.

Background: Unexplained exertional dyspnoea without significant elevation of natriuretic peptides is common. One of the causes might be early heart failure with preserved ejection fraction (HFpEF).

Aims: This study aimed to characterize patients with exertional dyspnoea and normal/near-to-normal N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with regard to early stages of HFpEF and non-cardiac causes.

Casz1 and Znf101/Zfp961 differentially regulate apolipoproteins A1 and B, alter plasma lipoproteins, and reduce atherosclerosis.

High apolipoprotein B-containing (apoB-containing) low-density lipoproteins (LDLs) and low apoA1-containing high-density lipoproteins (HDLs) are associated with atherosclerotic cardiovascular diseases. In search of a molecular regulator that could simultaneously and reciprocally control both LDL and HDL levels, we screened a microRNA (miR) library using human hepatoma Huh-7 cells. We identified miR-541-3p that both significantly decreases apoB and increases apoA1 expression by inducing mRNA degradation of 2 different transcription factors, Znf101 and Casz1.

Current approach to diagnosis and management of low-phospholipid associated cholelithiasis syndrome.

Purpose Of Review: Low phospholipid-associated cholelithiasis (LPAC) syndrome is a rare genetic form of intrahepatic cholesterol lithiasis, affecting mainly young adults. This review describes the recent advances in genetic and clinical characterization, diagnosis and management of LPAC syndrome.

Recent Findings: Recent publications report data from several retrospective cohorts.

Drug Development.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.

Drug Development.

Background: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.

Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.

Drug Development.

Background: Tau proteins aggregate in a number of neurodegenerative disorders known as tauopathies. Various studies have highlighted the role of microtubule-binding domains in the intracellular aggregation of Tau protein.

Method: Using a library of synthetic VHHs humanized in collaboration with Hybrigenics, we have developed a number of anti-tau VHHs.

Drug Development.

Background: Oral ALZ-801 (valiltramiprosate), a brain-penetrant agent that inhibits amyloid-oligomer formation is being evaluated in a fully enrolled APOLLOE4 Phase 3 trial in APOE4/4 homozygotes with Early Alzheimer's disease (AD). ALZ-801 effects on plasma AD biomarkers were evaluated in a 104-week Phase 2 study in APOE4-carriers with CSF+ AD biomarkers. APOE4 is a major risk factor for amyloid-related imaging abnormalities (ARIA) in AD patients.

Drug Development.

Background: Progranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer's disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation.

Drug Development.

Background: Chronic innate neuroinflammation mediated by microglia and astrocytes in response to Aβ and pathological Tau species is a cardinal feature of AD that contributes to disease pathogenesis. Accumulating evidence now also highlight an instrumental role of T cells and peripheral-central immune crosstalk in the pathophysiology of AD. Both preclinical and clinical reports suggest the potential therapeutic interest of peripheral immunomodulatory approaches aimed at amplifying regulatory T cells (Tregs), e.

Dementia Care Research and Psychosocial Factors.

Background: Using artificial intelligence approaches enable automated assessment and analysis of speech biomarkers for Alzheimer's disease, for example using chatbot technology. However, current chatbots often are unsuitable for people with cognitive impairment. Here, we implemented a user-centred-design approach to evaluate and improve usability of a chatbot system for automated speech assessments for people with preclinical, prodromal and early dementia.

Dementia Care Research and Psychosocial Factors.

Background: The progressive nature of dementia and the complex needs means that people living with dementia require tailored approaches to address their changing care needs over time. These include physical multimorbidity, psychological, behavioural, and cognitive symptoms and possible risks arising from these and helping family caregivers. However, provision of these interventions is highly variable between and within countries, partly due to uncertainty about their efficacy and scarce resources.

Dementia Care Research and Psychosocial Factors.

Background: Data from high-income countries (HICs) suggest a decline in age-specific incidence rates of dementia. However, this has happened primarily in HICs, with low- and middle- income countries (LMICs) facing two main challenges: a higher burden of risk factors and, in general, a faster ageing population. Most people with dementia live in LMICs, and this is set to increase, thus requiring urgent and robust action to prevent, treat and support people with dementia and their families.

Dementia Care Research and Psychosocial Factors.

Background: Our authors from around the world met to summarise the available knowledge, decide which potentially modifiable risk factors for dementia have compelling evidence and create the most comprehensive analysis to date for potentially modifiable risk factors to inform policy, give individuals the opportunity to control their risks and generate research.

Method: We incorporated all risk factors for which we judged there was strong enough evidence. We used the largest recent worldwide meta-analyses for risk factor prevalence and relative risk and if not available the best data.

Dementia Care Research and Psychosocial Factors.

Background: Facial emotion recognition testing in Alzheimer's disease (AD) patients has been identified as key for early detection and as a marker for disease progression. Emotion recognition remains one of the most difficult domains to assess in culturally diverse populations due to a lack of culturally adapted tools. This study assessed the feasibility of a cross-cultural test for emotion recognition, the TIE-93, in French and North African populations living in France.

Dementia Care Research and Psychosocial Factors.

Background: In sub-Saharan Africa (SSA), the number of people living with dementia is expected to double every 20 years, from 2.7 to 7.6 million.