Publications by authors named "R Sweet"
Article Synopsis
- The voltage-gated calcium channel (VGCC) is made up of an α1 subunit and three auxiliary subunits, with the β subunit being crucial for moving the α1 subunit to the cell membrane and is extensively studied in calcium signaling.
- VGCCs play a critical role in calcium ion movement within neurons, influencing processes like dendritic spine plasticity, with dysfunction in this signaling linked to neurodevelopmental disorders such as schizophrenia.
- Overexpressing the β4 subunit in a mouse model reduced the density of small dendritic spines, with notable sex differences in this effect, indicating that interactions with other VGCC subunits, like β1b in males, may help protect against this reduction.
Preservation of dendritic spines is a putative mechanism of protection against cognitive impairment despite development of Alzheimer Disease (AD)-related pathologies. Aging, the chief late-onset AD risk factor, is associated with dendritic spine loss in select brain areas. However, no study to our knowledge has observed this effect in precuneus, an area selectively vulnerable to early accumulation of AD-related pathology.
View Article and Find Full Text PDFMicrotubule-associated protein 2 (MAP2) is a crucial regulator of dendritic structure and neuronal function, orchestrating diverse protein interactions within the microtubule network. We have shown MAP2 is hyperphosphorylated at serine 1782 (S1782) in schizophrenia and phosphomimetic mutation of S1782 in mice (MAP2) is sufficient to impair dendritic architecture. We sought to determine how this hyperphosphorylation affects the MAP2 interactome to provide insights into the disorder's mechanisms.
View Article and Find Full Text PDFBackground: Few rare variants have been identified in genetic loci from genome-wide association studies (GWAS) of Alzheimer's disease (AD), limiting understanding of mechanisms, risk assessment, and genetic counseling.
Methods: Using genome sequencing data from 197 families in the National Institute on Aging Alzheimer's Disease Family Based Study and 214 Caribbean Hispanic families, we searched for rare coding variants within known GWAS loci from the largest published study.
Results: Eighty-six rare missense or loss-of-function (LoF) variants completely segregated in 17.
Introduction: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD). There are no effective treatments targeting these symptoms.
Methods: To facilitate identification of causative mechanistic pathways, we initiated an effort (NIH: U01AG079850) to collate, harmonize, and analyze all available NPS data (≈ 100,000 samples) of diverse ancestries with whole-genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP).