Alzheimer's disease research and treatments

Genetic architecture of Alzheimer's disease is enriched in peripheral immune and metabolic programs

This study identifies peripheral immune and metabolic tissues as key contributors to Alzheimer's disease genetic risk, independent of brain-specific factors.

Disease-specific tangle immunophenotypes distinguish hippocampal vulnerability in Alzheimers disease and Parkinsons disease dementia

The paper identifies disease-specific tau immunophenotypes in hippocampal subfields of Alzheimer's disease and Parkinson's disease dementia.

Myelin maturation failure and oligodendrocyte precursor loss underlie default mode network disruption in a humanized APP knock-in model of Alzheimers disease

This study identifies myelin maturation failure and oligodendrocyte precursor loss as underlying causes of default mode network disruption in an Alzheimer's disease mouse model.

Population-scale subcellular proteomics reveals intracellular remodelling across the Alzheimer's disease-resilience spectrum

The paper uses subcellular proteomics to identify disease-associated protein localization shifts in Alzheimer's disease across the resilience spectrum, revealing insights beyond abundance-based proteomics.

Secondary nucleation drives polymorph diversity in hIAPP amyloids

This study shows that secondary nucleation increases polymorphic diversity in hIAPP amyloids, and molecular chaperones can steer aggregation toward a monomorphic state.

A proteomic analysis of the PHF-forming tau fragment (tau297-391) following uptake into differentiated human neuronal SHSY5Y cells

The paper investigates the proteomic response in neuronal cells after exposure to a tau fragment, identifying pathways linked to tau pathology development.

A Systems Neuroscience Approach Identifies IL1B-CASP3 Signaling as a Molecular Link Between Polystyrene Exposure and Alzheimer's Disease

Spatially resolved mapping of tau amplification rates via differentiable simulation of prion-like propagation

The paper infers spatially resolved tau amplification rates from tau PET data using a differentiable reaction-diffusion framework and links these rates to amyloid PET and gene expression patterns.

A pathological phosphorylation pattern enhances taucooperativity on microtubules and facilitates tau filamentassembly

The paper investigates how specific phosphorylation patterns of tau affect microtubule binding, cooperativity, and filament assembly in tauopathies, revealing that pattern, not level, drives filament formation.

Population-specific transcriptional-state remodeling of cortical and hypothalamic neurons in Alzheimer's disease

The paper identifies population-specific transcriptional changes in neurons across Alzheimer's disease models and human samples, revealing molecular remodeling not captured by population representation alone.

Clinically Relevant Biomarkers of Alzheimers Disease Are Associated with Age and Cortical Atrophy in Chimpanzees (Pan troglodytes)

The paper examines age-related changes in Alzheimer's disease biomarkers and their association with cortical atrophy in chimpanzees, finding significant correlations between biomarkers and brain aging phenotypes.

β-Arrestin2 Drives Sex-Specific Akt/GSK3β Signaling, Aβ Pathology, and Cognitive Decline in Alzheimers Disease Mice

This study shows that β-arrestin2 deficiency has sex-specific effects on Aβ pathology, cognition, and autophagy in Alzheimer's disease mice, with male-specific reductions in pathology and cognitive decline.

Genomics link obesity and type 2 diabetes to Alzheimers disease to unveil novel biological insights

This study links obesity and type 2 diabetes to Alzheimer's disease through genetic and transcriptomic analyses, identifying shared pathways and potential drug targets.

cis-gamma-Amino-L-proline peptides as chemical probes of amyloidogenic processing in neurons and APP/PS1 mice

This study designs and evaluates cis-gamma-amino-L-proline peptides as modulators of amyloid-beta production, showing reduced Aβ levels and improved cognition in APP/PS1 mice.

Cryo-EM structure of pro-aggregant P301L/S320F double-mutant tau filaments formed in mouse brains following peripheral AAV delivery

The paper reports a cryo-EM structure of P301L/S320F double-mutant tau filaments induced in mice via peripheral AAV delivery, revealing a novel filament fold distinct from known tauopathies.

Optimized AAV to express the unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease features in mouse models

This study develops a next-generation AAV vector expressing optimized XBP1s to improve proteostasis, reducing Alzheimer's disease features in mouse models.

TMEM106B haplotypes show distinct associations with tau and TDP-43 pathologies in the aging brain

The paper examines TMEM106B haplotypes and their associations with tau and TDP-43 pathologies in aging brains using integrated multi-omics data.

Classification of ACE variants related to Alzheimer's disease (AD): the ACE mutations -- AD browser

The paper creates a database of ACE variants linked to Alzheimer's disease, estimates their population frequency, and links them to reduced blood ACE levels.

Molecular Disease Stages of Oligodendrocytic and Neuronal Tau Burden in Progressive Supranuclear Palsy

This paper identifies molecular progression trajectories in PSP by integrating snATACseq and snRNAseq data with tau pathology, revealing cell-type-specific transcriptional changes and glial reactivity.

Polymorphic structures of rapidly twisting 40-residue amyloid-β fibrils

The paper characterizes three polymorphic structures of rapidly twisting Aβ40 fibrils using cryo-EM, revealing differences in twist handedness, symmetry, and conformation despite similar cross-over distances.

Sex-divergent trajectories of hippocampal and cortical NMDA receptor density across the Alzheimer 's disease continuum

The paper examines sex differences in NMDA receptor density across Alzheimer's disease stages and finds sex-specific changes in mild cognitive impairment.

17α-Estradiol Confers Limited Protection Against APOE4 Phenotypes in Middle-Aged Female Mice

This study tests if 17α-estradiol benefits APOE4 females similarly to males, finding limited CNS improvements but some metabolic benefits in APOE4 females.

Mechanisms of resilience to autosomal dominant Alzheimer's disease via oligogenic modulation of rare variants in the entorhinal cortex

Peripheral T-cell co-signalling states mark vulnerability and resilience to cerebral Aβ pathology

The paper identifies T-cell co-signalling states linked to vulnerability and resilience to cerebral Aβ pathology in Alzheimer's disease.

APP Dosage and Extracellular Domain Variants Drive Distinct Defects in Neurogenesis modeled in Down Syndrome iPS cells

This study investigates how APP dosage and extracellular domain variants affect neurogenesis in Down Syndrome iPSCs, finding distinct defects in terminal differentiation and neurite outgrowth.

Tau-induced mitochondrial reverse electron transport drives neurodegeneration

This study shows that tau regulates mitochondrial reverse electron transport, leading to ROS production and neurodegeneration, and identifies potential therapeutic targets.

Plaque-associated oligodendrocyte proteostatic failure underlies myelin loss in Alzheimers disease

This study shows that amyloid plaques disrupt oligodendrocyte proteostasis, leading to myelin loss in Alzheimer's disease.

COGNITIVE DETERIORATION IS REVERSED BY AN INSULIN-LIKE GROWTH FACTOR 1 SENSITIZER IN A MOUSE MODEL OF ALZHEIMER DISEASE

A small molecule IGF-1 sensitizer reversed cognitive decline and reduced amyloid-beta levels in a mouse model of Alzheimer's disease.

CXCL10 drives female-specific tau pathology progression and defines sex-dependent vulnerability in tauopathy model mice

This study identifies CXCL10 as a driver of female-specific tau pathology progression in tauopathy model mice, revealing a sex-dependent mechanism independent of T cell or glial activation.

Fibril Paint: a class of amyloid-targeting peptides

This paper introduces FibrilPaints, a modular peptide system for selective amyloid binding and manipulation, showing that sequence variations affect binding affinity while allowing functional modifications.