Alzheimer's Imaging Consortium.

Background: Anxiety is prevalent among cognitively unimpaired older adults and is associated with accelerated amyloid-ß-related cognitive decline and incident cognitive impairment. Investigating these mechanisms is challenging due to low pathologic burden, high individual variability, and subsyndromal level of symptoms. Recently, brain networks involved in AD were successfully localized by mapping the brain connectivity of atrophy patterns associated with memory impairment and delusions.

Alzheimer's Imaging Consortium.

Background: Financial exploitation vulnerability (FEV) denotes the risk for falling victim to financial fraud and older adults reportedly lose an estimated $36 billion annually to scams. Socioemotional and cognitive impairments are potential risk factors for FEV in older adults with dementia. The present study examines whether the socioemotional measures of sensitivity to unfairness and self-unawareness of socioemotional dysfunction and brain atrophy are associated with increased risk for FEV in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD).

Alzheimer's Imaging Consortium.

Background: Tangle burden, one of the hallmarks of Alzheimer's Disease, is thought to accumulate and spread throughout the brain in a distinctive pattern starting from the entorhinal cortex following Braak stages as characterized in neuropathological studies. Longitudinal tau PET allows us to investigate in vivo the tau spread in an individual and substantial heterogeneity has been observed in the pattern of tau spread. In this analysis, we examine the statistical power of tau PET measurements in tracking disease progression using data from the ADNI cohort.

Alzheimer's Imaging Consortium.

Background: Neuropathological studies indicate that locus coeruleus(LC) volume decreases in Alzheimer's disease(AD) by 8% at each stage, (from Braak 0-1), whereas in normal aging, the LC remains unchanged. These changes make LC volumetry by neuroimaging a promising way to track AD progression even before symptoms appear. However, LC's small size and location make it prone to imaging artifacts.

Alzheimer's Imaging Consortium.

Background: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

Alzheimer's Imaging Consortium.

Background: Neuritic plaques with fibrillar beta-amyloid (Aß) peptides and tau-protein neurofibrillary tangles, hallmark features of Alzheimer's disease (AD) pathology, have been concomitantly associated with white matter (WM) integrity loss, while a unique effect of each pathology on WM integrity in a more demographically diverse population remains unknown.

Method: To examine the degree to which each pathology affects WM integrity in a more diverse non-demented cohort, Aß and tau PET, diffusion-weighted imaging (DWI), and cognition (memory and executive function composites) were examined from the U.S.

Alzheimer's Imaging Consortium.

Background: Frontotemporal lobar degeneration (FTLD) is defined neuropathologically by misfolded tau (FTLD-tau) or TAR DNA-binding protein of 43 kDa (FTLD-TDP). However, we lack biomarkers that can distinguish them in vivo which is a major barrier to effective disease-modifying treatment trials. Based on neuropathological evidence of distinct patterns of cellular degeneration, more prominent in white matter (WM) for FTLD-tau relative to FTLD-TDP, we hypothesized that diffusion MRI (dMRI) measures of white matter microstructure would help dissociate FTLD-tau and FTLD-TDP during life.

Alzheimer's Imaging Consortium.

Background: Changes in brain network organization are influenced by aging. Accumulation of amyloid-beta (Aß) and neurodegeneration in the neocortex are also expected to alter neuronal networks. Therefore, we examined the relationship between aging and brain functional connectivity (FC), as well as the effect of brain Aß on this relationship.

Alzheimer's Imaging Consortium.

Background: Postmortem MRI allows brain anatomy to be examined at high-resolution linking pathology with morphometric measurements. However, automated methods for analyzing postmortem MRI are not well developed. We present a deep learning-based framework for automated segmentation of cortical mantle, subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities (WMH), and normal appearing white matter in (n = 135) postmortem human brain tissue specimens (Table 1) imaged at 0.

Impact of PM, relative humidity, and temperature on sleep quality: a cross-sectional study in Taipei.

Introduction: TWe investigated impacts of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM), relative humidity (RH), and temperature on sleep stages and arousal.

Materials And Methods: A cross-sectional analysis involving 8,611 participants was conducted at a sleep center in Taipei.

Evaluating the Use of a 3D Exoscope to Improve Ergonomics in Cleft Surgery.

The aim of this study was to investigate and compare the technical feasibility, ergonomics, and educational value of the 3D exoscope in comparison with traditional and prism loupes in cleft surgery. A variety of cleft and pharyngeal operations were performed with the VITOM 3D exoscope (Karl Storz GmbH, Tuttlingen, Germany), traditional/prism loupes, and microscope. The cervical neck angulation of the operating surgeon was recorded in real-time with an inertia measurement unit system (Mbient, San Francisco, USA) and experiences of the surgeon and assistant were prospectively evaluated with 5-point Likert scales.

KRASG12D drives immunosuppression in lung adenocarcinoma through paracrine signaling.

Lung cancer is the leading cause of cancer deaths in the United States. New targeted therapies against the once-deemed undruggable oncogenic KRAS are changing current therapeutic paradigms. However, resistance to targeted KRAS inhibitors almost inevitably occurs; resistance can be driven by tumor cell-intrinsic changes or by changes in the microenvironment.

The CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.

The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel. We examined if CLCA1/TMEM16A had a role in DKD.

Drug Development.

Background: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.

Drug Development.

Background: The accumulation of amyloidogenic proteins is recognized as a primary biomarker, initiator of pathology, and a potential therapeutic target for Alzheimer's disease (AD). An unbiased screening of a small molecule library was conducted to identify new chemical compounds exhibiting amyloid-dissociative properties.

Method: The ability of aryloxypropanolamine derivatives to dissociate amyloid-β (Aβ) aggregates was evaluated through in vitro assays.

Drug Development.

Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.

Drug Development.

Background: Elevation of cerebrospinal fluid (CSF) tau is a feature of Alzheimer's disease (AD) and is being explored as a biomarker of AD and other tauopathies. The aim of this study was to elucidate the in vivo effects of DA-7503, a potent and selective tau aggregation inhibitor, and its pharmacodynamics on CSF tau in transgenic mouse models of Alzheimer's disease and primary tauopathies.

Method: TauP301L-BiFC mice expressing full-length human tau with the P301L mutation were orally administrated with DA-7503 for 1 month.

Drug Development.

Background: Neurofibrillary tangles (NFTs), along with amyloid beta plaque, are neuropathological aggregates of Alzheimer's Disease (AD). Hyperphosphorylated tau is responsible for the NFTs formation and further neurodegeneration in AD. The hippocampal region and the entorhinal cortex (EC) have been a major focus of AD research because the deposits of hyperphosphorylated tau protein and NFT in these regions are correlated with memory deficits.

Drug Development.

Background: Accumulating evidence suggests that the presynaptic protein α-synuclein (α-syn), is involved in the pathophysiology of AD and elevated in the cerebrospinal fluid (CSF). The role of Natural Killer (NK) cells of the innate immune system in AD has largely been overlooked. In a murine model, depletion of NK cells augmented the accumulation of pathological α-syn.

Drug Development.

Background: VY-TAU01 is a recombinant humanized IgG4 monoclonal antibody (mAb) directed against pathological tau for the treatment of patients with mild dementia or mild cognitive impairment due to Alzheimer's disease (AD). Both VY-TAU01 and its parental mouse IgG1 mAb Ab-01 target an epitope in the C-terminus of tau, bind pathological tau with high affinity and selectivity over wild-type tau, block paired helical filament seed-induced tau aggregates in vitro, and selectively stain tau tangles in AD and P301S mouse (C57/B6J-Tg[Thy1-MAPT*P301S]2541Godt) brain. Ab-01 robustly inhibits seeding and propagation of pathological tau in a P301S mouse seeding model.

Drug Development.

Background: Recruiting large numbers of study participants for Alzheimer's Disease (AD) drug trials remains a significant challenge in need of more effective approaches. Advertising can be an effective way to reach large numbers of prospective participants, but can suffer from low attendance rates. This study examined the relationship between the initial behaviors of prospective AD trial participants who did not attend their first scheduled appointment and their overall likelihood of eventually attending an in-person consultation.

Drug Development.

Background: Neurodegenerative diseases, including Alzheimer's disease (AD), have been long thought to be independent of the peripheral immune system, but their pathogenesis status is functionally influenced by various T cell subsets in the periphery. Especially Treg cells are emerging as an important dynamic population in the brain, but the detailed immunological molecular and cellular processes are poorly characterized METHOD: We reported that the cell surface protein Lrig1 is enriched in Treg cells and is an essential regulator of the functions of Treg cells in vitro and in vivo. To evaluate the functional importance of Treg cells in AD pathogenesis, the modulating mAb specific to Lrig1 (GTC 310-01) via intravenous injection route was administered into 5xFAD or 6xTg mice, the genetic mouse model of AD, and the various AD symptoms were investigated.

Drug Development.

Background: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.

Method: We compared scores on the Research Attitudes Questionnaire (RAQ) of individuals enrolled in two recruitment registries: the UCI Consent to Contact [C2C (N = 4818)] and DS-Connect (N = 976).

Dementia Care Research and Psychosocial Factors.

Background: People with dementia of all ages have a human right to equal access to quality health care. Despite evidence regarding its effectiveness, many people living with dementia lack access to evidence-based rehabilitation for promoting function and quality of life. The aims of this study were to 1) explore barriers to access to dementia rehabilitation; and 2) identify solutions which improve access to rehabilitation.

Dementia Care Research and Psychosocial Factors.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive emerging tool to modulate brain activities and functional connectivity in various neuropsychiatric disorders. rTMS combined with cognitive training (rTMS-COG) has been showing cognitive enhancing effects compared to those of placebo in mild Alzheimer's disease (AD) in some previous studies. However, there is not much research to conclude how much each rTMS or COG contributes to therapeutic cognitive effects.