Alzheimer's disease research and treatments

Templated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoids

Cortical organoids from healthy human iPSCs, seeded with Alzheimer brain tau, form three-repeat tau filaments that cryo-EM shows are identical to Alzheimer paired helical filaments and need endogenous tau.

A water-pinning hotspot drives templated tau aggregation

In a minimal tau fibril model, residue 300/301 binds incoming peptide first and carries the most release-prone hydration water. Spin-labelling site 300 impairs locking and suppresses seeded growth.

Mapping Alzheimer's neuropathology signatures to the whole brain transcriptome using machine learning data fusion

Cell type-specific logistic regression estimators trained on 427 ROSMAP prefrontal donors project Braak- and β-amyloid-like transcriptomic signatures onto the 108-region Siletti atlas, flagging brainstem, hypothalamic and rostral hippocampal regions.

Human-mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome

Alzheimer's mouse model proteomes capture 30% (amyloid-only models) to 42% (adding tau and splicing models) of consensus human AD protein changes; in 5xFAD, plaques slow degradation of plaque-associated proteins.

Cryo-EM Structures of Amyloid-β 42 Filaments from Human Brain

Cryo-EM shows brain-derived Aβ42 filaments adopt two related S-shaped protofilament folds: Type I dominates sporadic Alzheimer's, Type II familial Alzheimer's, other disorders and App^NL-F knock-in mice.

Structure-based Classification of Tauopathies

Cryo-EM structures sort four-repeat tauopathies into three-layered (PSP, GGT, LNT) and four-layered (CBD, AGD, ARTAG, MAPT intron 10 mutations) tau folds, grounding a hierarchical structure-based classification.

Genome-wide meta-analysis, fine-mapping, and integrative prioritization identify new Alzheimer's disease risk genes

Meta-analysing UK Biobank family-history GWAS with diagnosed-AD GWAS yields 37 loci, four novel (NCK2, TSPAN14, SPRED2, CCDC6); fine-mapping, colocalisation and network scoring prioritize causal genes.