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A PKCeta missense mutation enhances Golgi-localized signaling and is associated with recessively inherited familial Alzheimer's disease

2 months 2 weeks ago
The identification of Alzheimer's disease (AD)-associated genomic variants has provided powerful insight into disease etiology. Genome-wide association studies (GWASs) of AD have successfully identified previously unidentified targets but have almost exclusively used additive genetic models. Here, we performed a family-based GWAS of a recessive inheritance model using whole-genome sequencing from families affected by AD. We found an association between AD risk and the variant rs7161410, which is...
Maria Celeste Gauron

Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinson's disease-linked LRRK2-mutant mice

2 months 2 weeks ago
Parkinson's disease is associated with activating mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2), which suppresses primary cilia formation in cholinergic and parvalbumin interneurons and astrocytes in the striatum. As a result, there is a decrease in the production of neuroprotective glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), which normally support the viability of dopaminergic neurons. MLi-2 is a brain-penetrant, selective, and now experimental...
Ebsy Jaimon

Association between self-reported multimorbidity and longitudinal brain Abeta deposition in Alzheimer's disease

2 months 2 weeks ago
Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer's disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of...
Xian-Le Bu

Integrated dopamine sensing and 40 Hz hippocampal stimulation improves cognitive performance in Alzheimer's mouse models

2 months 2 weeks ago
Hippocampal degeneration and reduced dopamine levels in Alzheimer's disease are associated with severe memory and cognitive impairments. However, the lack of multifunctional in situ neural chips has posed challenges for integrated investigations of Alzheimer's disease pathophysiology, dopamine dynamics, and neural activity. Therefore, we developed NeuroRevive-FlexChip, a flexible neural interface capable of precise electrical modulation and simultaneous in situ monitoring of dopamine levels and...
Shiya Lv