Ian R. Mackenzie

Cerebrospinal fluid YWHAG:NPTX2 ratio predicts clinical severity and future phenoconversion in frontotemporal lobar degeneration

The paper identifies the CSF YWHAG:NPTX2 ratio as a biomarker for predicting clinical severity and phenoconversion in FTLD, showing strong correlation with disease progression and improved trial design potential.

Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15

This study identifies distinct TAF15 amyloid filament structures in different FTLD-FET subtypes, leading to the renaming of the disease group as FTLD-TAF15.

Relationship between therapeutic activity and preferential targeting of toxic soluble aggregates by amyloid-beta-directed antibodies

The paper examines how the binding selectivity of amyloid-beta antibodies to toxic oligomers correlates with therapeutic efficacy and reduced risk of adverse effects in Alzheimer's disease.

Rational Generation of Monoclonal Antibodies and Intrabodies Selective for Pathogenic TDP-43

This paper generates monoclonal antibodies and intrabodies that selectively target misfolded TDP-43 aggregates in disease, showing they inhibit transmission and promote degradation in cell models.

A 3D human iPSC-derived multi-cell type neurosphere system to model cellular responses to chronic amyloidosis

This paper uses a 3D human iPSC-derived neurosphere model to study how microglia modify cellular responses to chronic amyloidosis, revealing their role in reducing neurotoxicity and regulating AD-associated gene expression.

Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia

This study examines sex differences in clinical progression of autosomal dominant frontotemporal dementia, finding females show more rapid declines in symptomatic stages and less sensitive NfL prognostic value.

Molecular signatures of altered energy metabolism and circadian rhythm perturbations in a model of extra-nigral Synucleinopathy.

This study uses spatial transcriptomics to analyze aSyn pathology in mice, revealing metabolic and circadian disruptions at different stages of disease progression.

Reduced progranulin increases tau and alpha-synuclein inclusions and alters phenotypes of tauopathy mice via glucocerebrosidase

This study shows that reduced progranulin increases tau and alpha-synuclein inclusions and worsens tauopathy mouse phenotypes via glucocerebrosidase.

Genome-wide association study of autopsy-confirmed Multiple System Atrophy identifies common variants near ZIC1 and ZIC4

α-Synuclein pathology in Parkinson disease activates homeostatic NRF2 anti-oxidant response

The paper shows that α-synuclein pathology in Parkinson's disease activates the NRF2 anti-oxidant response, suggesting it could be a therapeutic target.

CXCR4 involvement in neurodegenerative diseases

The paper identifies a genetic variant near CXCR4 associated with increased risk for PSP and PD, showing dysregulation of CXCR4 and microglia-related genes in neurodegenerative diseases.

Immune-related genetic enrichment in frontotemporal dementia

This study identifies genetic overlaps between frontotemporal dementia and immune-mediated diseases, finding strong enrichment with rheumatoid arthritis and moderate enrichment with other immune conditions.