Publications by authors named "Emily R Mahoney"
The vascular endothelial growth factor (VEGF) signaling family has been implicated in neuroprotection and clinical progression in Alzheimer's disease (AD). Previous work in postmortem human dorsolateral prefrontal cortex demonstrated that higher transcript levels of VEGFB, PGF, FLT1, and FLT4 are associated with AD dementia, worse cognitive outcomes, and higher AD neuropathology. To expand prior work, we leveraged bulk RNA sequencing data, single nucleus RNA (snRNA) sequencing, and both tandem mass tag and selected reaction monitoring mass spectrometry proteomic measures from the post-mortem brain.
View Article and Find Full Text PDFApolipoprotein E4 (APOE-ε4), the strongest common genetic risk factor for Alzheimer's disease (AD), contributes to worse cognition in older adults. However, many APOE-ε4 carriers remain cognitively normal throughout life, suggesting that neuroprotective factors may be present in these individuals. In this study, we leverage whole-blood RNA sequencing (RNAseq) from 324 older adults to identify genetic modifiers of APOE-ε4 effects on cognition.
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- About 30% of elderly adults show no cognitive impairment at death despite having Alzheimer's disease pathology, which suggests exploring their resilience could lead to new treatments for Alzheimer's.
- The study focuses on understanding sex-specific genetic factors that contribute to resilience against Alzheimer's by analyzing cognitive data and genetic factors from a large cohort across multiple studies.
- The research identified a significant genetic variant on chromosome 10 that is linked to higher resilience scores specifically in females, suggesting that certain genes related to RNA processing may play a role in this resilience.
Article Synopsis
- Some people have signs of Alzheimer's disease but don't show any symptoms, which is called preclinical Alzheimer's disease.
- Researchers wanted to find out if certain genetic differences could help protect some people from brain damage related to Alzheimer's.
- They discovered that a specific gene (known as -ɛ4) makes some people lose brain volume (hippocampal atrophy) faster if they have high levels of a protein linked to Alzheimer's, while another gene variant showed different effects depending on the amount of that protein.
A practical, modular synthesis of targeted molecular imaging agents (TMIAs) containing near-infrared dyes for optical molecular imaging (OMI) or chelated metals for magnetic resonance imaging (MRI) and single-photon emission correlation tomography (SPECT) or positron emission tomography (PET) has been developed. In the method, imaging modules are formed early in the synthesis by attaching imaging agents to the side chain of protected lysines. These modules may be assembled to provide a given set of single- or dual-modal imaging agents, which may be conjugated in the last steps of the synthesis under mild conditions to linkers and targeting groups.
View Article and Find Full Text PDFAlzheimer's disease (AD) disproportionately affects certain racial and ethnic subgroups, such as African American/Black and Hispanic adults. Genetic, comorbid, and socioeconomic risk factors contribute to this disparity; however, the molecular contributions have been largely unexplored. Herein, we conducted a pilot proteomics study of postmortem brains from African American/Black and non-Hispanic White adults neuropathologically diagnosed with AD compared to closely-matched cognitively normal individuals.
View Article and Find Full Text PDFGenetic mechanisms underlying age-related cognitive decline and dementia remain poorly understood. Here, we take advantage of the Diversity Outbred mouse population to utilize quantitative trait loci mapping and identify Dlgap2 as a positional candidate responsible for modifying working memory decline. To evaluate the translational relevance of this finding, we utilize longitudinal cognitive measures from human patients, RNA expression from post-mortem brain tissue, data from a genome-wide association study (GWAS) of Alzheimer's dementia (AD), and GWAS results in African Americans.
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- About 30% of older adults have Alzheimer's disease-related brain changes but show no cognitive decline, indicating some individuals have genetic resilience.
- A large genome-wide association study (GWAS) involving over 5,100 participants identified genetic correlations between cognitive resilience metrics and factors like cognitive performance, education, and neuropsychiatric conditions, but not with Alzheimer's disease itself.
- Significant findings included a specific genetic variant on chromosome 18 (rs2571244) linked to protective factors against cognitive decline, suggesting that vascular risk, metabolism, and mental health may contribute to resilience in the face of Alzheimer's pathology.
Article Synopsis
- Genetic studies of Alzheimer’s disease typically focus on diagnosed cases, overlooking the genetic factors involved during the preclinical phase where symptoms haven't yet appeared.
- This research aimed to identify genetic factors linked to brain amyloidosis—the buildup of amyloid proteins in the brain—before Alzheimer’s symptoms become noticeable.
- The study analyzed data from over 4,300 participants across various cohort studies and discovered a new genetic locus related to amyloidosis, potentially aiding in early detection and intervention strategies.
Telomere length associations with cognition depend on Alzheimer's disease biomarkers.
Alzheimers Dement (N Y)
December 2019
Introduction: While telomere shortening, a marker of cellular aging, may impact the progression of age-related neurodegenerative diseases, its association with cognition is unclear, particularly in the context of Alzheimer's disease (AD) pathology.
Methods: Telomere, cognitive, and CSF data from 482 participants in the AD Neuroimaging Initiative (148 cognitively normal, 283 mild cognitive impairment, 51 AD) was leveraged to assess telomere length associations with cognition (measured by memory and executive function) and interactions with CSF amyloid-β, tau, and . Secondary analyses assessed brain volume and thickness outcomes.
A series of Cy5.5 dye analogs and targeted probes with net charges varied from -3 to 0 were synthesized by an optimized method, followed by comparing their spectral and photostability properties in saturated solutions of air, oxygen, and argon. The Cy5.
View Article and Find Full Text PDFVascular endothelial growth factor (VEGF) is associated with the clinical manifestation of Alzheimer's disease (AD). However, the role of the VEGF gene family in neuroprotection is complex due to the number of biological pathways they regulate. This study explored associations between brain expression of VEGF genes with cognitive performance and AD pathology.
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- Research into suction-feeding fishes illustrates how the integration of movement and food consumption is crucial, yet other scenarios may affect this integration differently.
- The paper suggests three contexts—behavioral flexibility in feeding, environmental physical demands during prey capture, and secondary adaptations in feeding behavior—aimed at prompting further research on how these factors influence the integration of functional traits across different species.