A case of chronic lymphocytic leukaemia with initial symptoms of cognitive impairment DOI Creative Commons
Baoye Ye,

Yilin Huang,

W. Lai

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Abstract Background: Chronic lymphocytic leukaemia (CLL) is a type of that often ignored in the initial stages. Slight fever, fatigue and night sweats are common presentations, but cognitive decline rare. Case presentation: A 69-year-old patient with early-stage CLL presented rapid decline. The was taken by his wife to seek medical attention our hospital. In reports from other hospitals, Mini-mental State Examination(MMSE) score 10, Montreal Cognitive Assessment(MoCA) zero since he could not cooperate. MRI revealed bilateral hippocampal atrophy. apolipoprotein E (APOE) gene test genotype e3/e4. blood also high leucocyte lymphocyte counts. Peripheral immunotyping subsequently performed, results abnormal monoclonal mature B cells. final diagnosis CLL. Discussion: To knowledge, memory loss rare primary phase However, we linked this patient’s impairment

Язык: Английский

Multifaceted roles of APOE in Alzheimer disease DOI
Rosemary J. Jackson, Bradley T. Hyman, Alberto Serrano‐Pozo

и другие.

Nature Reviews Neurology, Год журнала: 2024, Номер 20(8), С. 457 - 474

Опубликована: Июнь 21, 2024

Язык: Английский

Процитировано

31
Lifetime risk and projected burden of dementia DOI
Michael Fang, Jiaqi Hu, Jordan Weiss

и другие.

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

Процитировано

5
The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4 DOI
Femke M. Feringa,

Sascha J. Koppes-den Hertog,

Lian Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 3, 2024

Abstract Lipid changes in the brain have been implicated many neurodegenerative diseases including Alzheimer’s Disease (AD), Parkinson’s disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named Neurolipid Atlas, that pre-populated with novel human, mouse isogenic induced pluripotent stem cell (iPSC)-derived lipidomics for different diseases. We show iPSC-derived neurons, microglia astrocytes display distinct lipid profiles recapitulate vivo lipotypes. Leveraging multiple datasets, AD risk gene ApoE4 drives cholesterol ester (CE) accumulation human recapitulating CE measured brain. Multi-omic interrogation of revealed plays major role astrocyte interferon-dependent pathways such as immunoproteasome histocompatibility complex (MHC) class I antigen presentation. through enhanced esterification suppresses immune activation astrocytes. Our commons, available at neurolipidatlas.com, provides user-friendly tool knowledge base better understanding dyshomeostasis

Язык: Английский

Процитировано

9
Brain health clinics – An evolving clinical pathway? DOI Creative Commons
Anneka F Butters, Jonathan Blackman,

Hannah Farouk

и другие.

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100051 - 100051

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
The impact of rare genetic variants on Alzheimer disease DOI
Lara De Deyn, Kristel Sleegers

Nature Reviews Neurology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Язык: Английский

Процитировано

1
The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease DOI Creative Commons
Alessandro Padovani, Alice Galli,

Elena Bazzoli

и другие.

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION Growing evidence suggests a connection between insulin resistance and apolipoprotein E ( APOE ) genotype in Alzheimer's disease (AD) pathogenesis, but the mechanisms are unclear. We examined effects of on blood–brain barrier (BBB) integrity AD. METHODS BBB was measured 196 biologically‐confirmed non‐diabetic patients with AD evaluating CSF/serum albumin ratio, kappa lambda free light chains (FLCs). Insulin assessed using triglyceride–glucose index (TyG). The impact TyG integrity, its interaction genotypes, analyzed multivariate models. RESULTS Sixty‐four percent showed altered TyG, 21.8% classified as high TyG. subgroups were associated abnormalities, similar clinical biomarkers profile. A significant ε4/ε4 permeability found analyses. DISCUSSION is common feature correlates permeability, interacting synergistically genotype. Highlights well‐recognized risk factors for (AD). shows prevalence related to damage integrity. association (TyG) varies relation genotype; displayed higher permeability.

Язык: Английский

Процитировано

1
Sex-related differences in genetically determined Alzheimer’s disease DOI Creative Commons
Laura del Hoyo Soriano, Olivia Wagemann, Alexandre Bejanin

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Март 4, 2025

We reviewed the literature on sex differences in genetically determined Alzheimer’s disease (AD), focusing autosomal dominant AD (ADAD), Down syndrome-associated (DSAD), and APOE4 homozygosity, particularly regarding penetrance, symptom onset clinical progression, trajectories for markers of amyloidosis (A), tau pathology (T) neurodegeneration (N). Data suggests that onset, AT(N) biomarker are typically subtle populations. Noteworthy exceptions, such as increased later stages females while similar cognitive outcomes, suggest a potential differential reserve warrants further investigation. Additionally, interaction between APOE genotype reveals complex multifaceted effects DSAD, with implications ADAD remain underexplored. The smaller observed compared to sporadic offer insights into different underlying mechanisms Future research should prioritize sex-specific investigations AD, refining methodologies. This includes prioritizing longitudinal designs, adjustment key confounders, adherence guidelines.

Язык: Английский

Процитировано

1
The Glutamate/GABA‐Glutamine Cycle: Insights, Updates, and Advances DOI Creative Commons
Jens V. Andersen

Journal of Neurochemistry, Год журнала: 2025, Номер 169(3)

Опубликована: Март 1, 2025

ABSTRACT Synaptic homeostasis of the principal neurotransmitters glutamate and GABA is tightly regulated by an intricate metabolic coupling between neurons astrocytes known as glutamate/GABA‐glutamine cycle. In this cycle, take up from synapse convert these into glutamine. Astrocytic glutamine subsequently transferred to neurons, serving precursor for neuronal synthesis. The cycle integrates multiple cellular processes, including neurotransmitter release, uptake, synthesis, metabolism. All processes are deeply interdependent closely coupled energy Astrocytes display highly active mitochondrial oxidative metabolism several unique features, glycogen storage pyruvate carboxylation, which essential sustain continuous release. However, new roles oligodendrocytes microglia in recycling emerging. Malfunction can lead severe synaptic disruptions may be implicated brain diseases. Here, I review central aspects recent advances highlight how functionally connected critical functions First, overview glutamate, GABA, transport provided relation recycling. Then, reviewed, with a special emphasis on glial cells. Finally, discuss aberrant linked neurodegeneration disease, focusing astrocyte dysfunction lipid emerging pathological mechanisms. Instead viewing individual biochemical more holistic integrative approach needed advance our understanding modulates function both health disease. image

Язык: Английский

Процитировано

1
Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer’s Disease DOI Creative Commons
John A. Hey,

Susan Abushakra,

Kaj Blennow

и другие.

Drugs, Год журнала: 2024, Номер 84(7), С. 811 - 823

Опубликована: Июнь 20, 2024

ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aβ) aggregation and oligomer formation being studied in phase 2 trial APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid imaging biomarkers cognitive assessments.

Язык: Английский

Процитировано

7
Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders DOI Open Access
Sarfaraz K. Niazi, Zamara Mariam,

Matthias Magoola

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6683 - 6683

Опубликована: Июнь 18, 2024

Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies Alzheimer’s disease approved, dozens testing phase, and one was withdrawn, other halted, likely due efficacy issues. However, these outcomes should have been evident since cannot enter sufficiently blood–brain barrier (BBB) protectant. all products be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model tested quickly at a low cost applied bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, their paper demonstrates conjugating transferrin does not alter such amyloid-β (Aβ) α-synuclein. We also present selection conjugate designs will allow cleavage upon entering prevent exocytosis while keeping fragments connected enable optimal proteins. The identified readily returned patients lowest regulatory delays. These engineered manufactured recombinant engineering, mRNA technology, more affordable solution meet dire need effectively.

Язык: Английский

Процитировано

6