The Delicate Balancing of Pros and Cons in the Surgical Management of Hyperparathyroidism in a Young Female with Germline Variant in the CDC73 Gene.

Hyperparathyroidism-jaw tumor syndrome is a rare form of syndromic primary hyperparathyroidism. We describe a young female with a history of common precursor B acute lymphoblastic leukaemia who was diagnosed with overt primary hyperparathyroidism due to a pathogenic CDC73 variant (c.25C > T).

Primary tumor surgery in de novo metastatic breast cancer: Game-changer or misinterpretation?

The study titled "Primary tumor surgery in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium" opens an important discussion about the potential role of surgery in the treatment of de novo MBC; although the results are promising, they should be interpreted with caution given the limitations of the study design. The question remains whether surgery is truly a game-changer for all patients or whether its benefits are more nuanced depending on individual patient factors and disease characteristics. As the oncology community continues to explore this question, a modern breast surgeon should emphasize the importance of further prospective trials and personalized treatment strategies that consider not only surgery but also the growing arsenal of available systemic therapies.

Basic Science and Pathogenesis.

Background: In 43-63% of symptomatic Alzheimer's disease (AD) patients, there is an observed accumulation of misfolded alpha-synuclein (αSyn). Two primary αSyn subtypes have been identified based on the underlying spreading pattern of this pathology: caudo-rostral and amygdala-predominant. Interactions between pathological TDP-43, Tau, and αSyn can aggravate their spread and aggregation.

Basic Science and Pathogenesis.

Background: The brain is shielded from the peripheral circulation by central nervous system (CNS) barriers, comprising the well-known blood-brain barrier (BBB) and the less recognized blood-cerebrospinal fluid (CSF) barrier located within the brain ventricles. The gut microbiota represents a diverse and dynamic population of microorganisms that can influence the health of the host, including the development of neurological disorders like Alzheimer's disease (AD). However, the intricate mechanisms governing the interplay between the gut and brain remain elusive, and the means by which gut-derived signals traverse the CNS barriers remain unclear.

Basic Science and Pathogenesis.

Background: Microglia are central players in Alzheimer's Disease (AD) pathology, but analyzing microglia states in human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies.

Method: To circumvent these issues, here we collected 138,577 single cell expression profiles of human stem cell derived-microglia from a xenotransplantation model of AD.

Result: Xenografted human microglia adopt a disease-associated (DAM) profile similar to that seen in mouse microglia, but display a more pronounced HLA state, likely related to antigen presentation in response to amyloid plaques.

Basic Science and Pathogenesis.

Background: Astrocytes are a numerous and diverse glial subtype specialised to carry out distinct roles involving maintaining homeostasis and effective functioning of the nervous system. To do so effectively, they respond to and secrete various proteins. In addition, astrocytes have been linked to Alzheimer's disease (AD), where they are believed to become reactive and contribute to neuroinflammation.

Basic Science and Pathogenesis.

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) has been recently recognized as a cause of dementia in the elderly. LATE and Alzheimer's disease (AD) share similar clinical presentations, and their neuropathological changes-LATE-NC and ADNC-commonly co-occur in the brains of individuals with dementia. Frontotemporal degeneration (FTLD-TDP) represents another group of TDP-43-associated neurodegenerative diseases.

Basic Science and Pathogenesis.

Background: Published data have highlighted associations between Alzheimer's disease (AD) susceptibility loci and AD-related brain changes. The amyloid imaging to prevent AD (AMYPAD) consortium is a European collaboration consisting of several parent cohorts, four of which had raw genotype array data available. We sought to integrate and harmonise the genetic data, calculate AD polygenic risk scores (PRS), and investigate their association with global amyloid deposition.

Basic Science and Pathogenesis.

Background: BIN1 is a major susceptibility gene for AD and BIN1 protein interacts with Tau. However, the contribution of BIN1 and its isoforms to AD pathogenesis remains unclear. We recently described that human BIN1 isoform1 (BIN1iso1) induces an accumulation of early endosome vesicles leading to neurodegeneration in Drosophila retina and that the early endosome size regulation was conserved in human induced neurons.

Basic Science and Pathogenesis.

Background: While social and medical debate about the efficacy and safety of anti-Aβ immunotherapy is ongoing, one thing that emerged is that we have little understanding of the working mechanisms of these antibodies and this lack of knowledge complicates the interpretation of the clinical results. Here, we aimed to establish if microglia are required for the efficacy of Lecanemab, one of the most promising FDA-approved disease-modifying therapy for AD (Van Dyck et al. N Engl J Med 2023).

Basic Science and Pathogenesis.

Background: Inflammation is central to Alzheimer Disease (AD), as astrocyte reactivity accompanies the appearance of Aβ and phosphorylated tau (Bellaver et al., 2023). As expected, therefore, AD patients have elevated levels of CSF inflammatory cytokines (Onyango et al.

Basic Science and Pathogenesis.

Background: While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-b (Aβ) progression remains unknown.

Method: Using the Baltimore Longitudinal Study of Aging (BLSA; n = 196; mean follow-up: 5 years/4 scans), we identified immune-related proteins in plasma (candidate proteins) related to rates of change in cortical Aβ levels, as measured by C-PiB PET. Along with identifying genetic variants that contributed to candidate protein associations, characterizing their relationships with tau-PET and changes in ADRD biomarkers (Aβ, NfL, GFAP, pTau-181), and assessing their expression patterns in human microglia, we leveraged data from the Atherosclerosis Risk in Communities (ARIC) study to determine if changes in candidate protein levels precede Ab = β onset (n = 272), and whether they predict 20-year dementia risk during mid-life (n = 11,596) and 8-year dementia risk during late-life (n = 4,288).

Basic Science and Pathogenesis.

Background: Apolipoprotein E (APOE) ε4 is a significant genetic risk factor for late-onset Alzheimer's Disease and appears to be closely related with brain amyloidosis. Current identification methods for APOE ε4 carriers are mostly based on genotyping which cannot always predict the specific ApoE protein isoform. We present a case study of a sample with a discordant result for genotype compared to the protein isoform (proteotype) and we reflect on possible implications for future applications.

Basic Science and Pathogenesis.

Background: Microglial cells have emerged as key players in the pathogenesis of Alzheimer's disease (AD). They act as a first line defense and fulfil a crucial role during brain development and circuit homeostasis. Microglia are involved in the removal of debris, control neural activity, regulate synaptic plasticity, and synapse pruning.

Basic Science and Pathogenesis.

Background: As neurodegenerative diseases advance, postmitotic neurons are affected by disturbed proteostasis and the accumulation of misfolded proteins. This renders neurons sensitive to cell death, ultimately leading to progressive neuron loss. Multiple studies show the involvement of distinct pathways of regulated cell death (RCD) in neurodegenerative diseases, such as necroptosis.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the primary cause of dementia, characterized by early amyloid beta accumulation, subsequent tau pathology, and eventually synaptic and neuronal loss. Sleep disturbances, a clinical phenotype in AD, are linked to amyloid beta and impaired protein clearance. However, the influence of tau pathology on sleep is less explored.

Rotavirus vaccine coverage, completion, and compliance: A systematic literature review.

Rotavirus, a leading cause of severe acute gastroenteritis in children, is largely preventable through immunization with two internationally licensed oral rotavirus vaccines (RVVs) included in national programs across over 100 countries. These RVVs are administered in either two (Rotarix™; 2D-RV) or three (RotaTeq®; 3D-RV) doses. We aimed to assess the global coverage, completion, and compliance of 2D-RV and 3D-RV in various settings, and to identify factors influencing vaccine coverage.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) brains commonly exhibit various co-morbid pathologies, with cerebral amyloid angiopathy (CAA) being the most prevalent, affecting 70-90% of patients. CAA can be restricted to medium and large vessels or extend to capillaries. Additionally, AD patients often show pathologies involving phosphorylated-TDP-43 (pTDP-43) and alpha-synuclein (αSyn), typically demonstrating an amygdala-predominant subtype.

Basic Science and Pathogenesis.

Background: ABCA7, an important risk gene for AD, encodes a transporter implicated in lipid transport and phagocytosis, and its disruptions have been linked to AD pathogenesis. However, the impact of these mutations on AD risk is complex due to their interaction with a multifaceted transcriptional architecture and cell type-specificexpression patterns. This study aims to analyze the intricate patterns of ABCA7 expression across diverse cell types, considering various ABCA7 genotypes in relation to AD patients and non-carrier controls, while also exploring the effects of ABCA7 mutations on transcriptome-wide gene expression.

Basic Science and Pathogenesis.

Background: Classical genome-wide association studies (GWAS) of Alzheimer's disease (AD), which successfully identified over 75 risk loci to date, are limited to the content of the imputation panels that typically do not cover all types of genetic variation, e.g., tandem repeats encompassing >55% of human genome.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a heterogenous disease with a strong heritability. Genetic studies are of irreplaceable value in elucidating the mechanisms that underly this disease. The classical genome-wide association studies (GWAS) rely on ever-increasing sample sizes and utilize clinical AD diagnosis to investigate genetic risk.

Basic Science and Pathogenesis.

Background: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relationship between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans.

Clinical Manifestations.

Background: The ability to discriminate very similar objects by implementing the binding between their multiple features is assumed to be supported by the medial temporal lobe (MTL). MTL is the first brain region that shows abnormal tau accumulation in Alzheimer's disease (AD). However, whether binding ability is impaired since the preclinical stage of AD and relates to MTL tau burden is not well-established.

Clinical Manifestations.

Background: While Alzheimer Disease (AD) patients' difficulty to recognize face identity (Werheid & Clare, 2007) has been mainly attributed to episodic and semantic memory impairments, these patients can also show abnormal difficulties at matching of unfamiliar faces for their identity, suggesting impaired perceptual function (Lavallée et al., 2016). However, since this latter evidence is based on explicit behavioural measures, the difficulties of AD patients can be due to many factors (e.