Publications by authors named "Delaney Flaherty"
In recent years, multiple groups have shown that what is currently thought of as "Alzheimer's Disease" (AD) may be usefully viewed as several related disease subtypes. As these efforts have continued, a related issue is how common co-pathologies and ethnicity intersect with AD subtypes. The goal of this study was to use a dataset constituting 153 pathologic variables recorded on 666 AD brain autopsies to better define how co-pathologies and ethnicity relate to established AD subtypes.
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- Genetic variants in the ABCA7 gene are linked to a higher risk of Alzheimer's disease (AD), but the exact function of ABCA7 in AD development remains uncertain.* -
- Researchers created a zebrafish model lacking the abca7 gene, revealing that ABCA7 is essential for the expression of neuropeptide Y (NPY) and other neurotrophic factors vital for brain health.* -
- Findings suggest that decreased NPY due to impaired ABCA7 function contributes to synaptic issues and a higher risk of AD, with clinical data showing a correlation between NPY levels and disease progression.*
The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy individuals with APOEε4 also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of APOEε4; however, these mechanisms are unknown. We hypothesized that APOEε4 carriers without dementia might carry genetic variations that could protect them from developing APOEε4-mediated AD pathology.
View Article and Find Full Text PDFMurine studies have highlighted a crucial role for immune cells in the meninges in surveilling the central nervous system (CNS) and influencing neuroinflammation. However, how meningeal immunity is altered in human neurodegeneration and its effects on CNS inflammation is understudied. We performed the first single-cell analysis of the transcriptomes and T cell receptor (TCR) repertoire of 104,635 immune cells from 55 postmortem human brain and leptomeningeal tissues from donors with neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease.
View Article and Find Full Text PDFThe risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the allele. Elderly cognitively healthy individuals with also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of ; however, these mechanisms are unknown. We hypothesized that carriers without dementia might carry genetic variations that could protect them from developing mediated AD pathology.
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- Alzheimer's disease (AD) is a complicated condition linked to cognitive decline and memory loss, with genetic variations playing a significant role in its development, although the exact mechanisms are still unclear.
- Researchers developed a knockout zebrafish model of an established AD-risk gene using CRISPR/Cas9, which exhibited decreased astroglial growth, synaptic density, and microglial levels when exposed to amyloid beta 42 (Aβ42).
- Findings from single-cell transcriptomics indicated that neuropeptide Y (NPY) signaling is crucial for neuronal and glial interaction, while clinical data in humans showed a correlation between reduced gene expression and advanced AD stages, along with genetic variations linked to the disease.
Recent murine studies have highlighted a crucial role for the meninges in surveilling the central nervous system (CNS) and influencing CNS inflammation. However, how meningeal immunity is altered in human neurodegeneration and its potential effects on neuroinflammation is understudied. In the present study, we performed single-cell analysis of the transcriptomes and T cell receptor repertoire of 72,576 immune cells from 36 postmortem human brain and leptomeninges tissues from donors with neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease.
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- Neurogenesis, which helps the brain stay resilient, decreases in Alzheimer's disease (AD), leading to reactive astrocytes that hinder neurogenesis; restoring neurogenesis could potentially counteract neurodegenerative effects.
- Researchers used a mouse model to explore the role of Nerve growth factor receptor (Ngfr) in promoting neurogenesis in astrocytes during AD, finding that Ngfr reduces a marker (Lcn2) associated with reactive astrocytes, thereby enhancing neurogenic outcomes.
- The study indicates that by boosting Ngfr expression, it's possible to decrease amyloid plaques and improve neurogenesis, suggesting that targeting astrocytes to promote their neurogenic potential could offer new therapeutic strategies for Alzheimer's disease.
The neuropathological landscape of Hispanic and non-Hispanic White decedents with Alzheimer disease.
Acta Neuropathol Commun
June 2023
Despite the increasing demographic diversity of the United States' aging population, there remain significant gaps in post-mortem research investigating the ethnoracial heterogeneity in the neuropathological landscape of Alzheimer Disease (AD). Most autopsy-based studies have focused on cohorts of non-Hispanic White decedents (NHWD), with few studies including Hispanic decedents (HD). We aimed to characterize the neuropathologic landscape of AD in NHWD (n = 185) and HD (n = 92) evaluated in research programs across three institutions: University of California San Diego, University of California Davis, and Columbia University.
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