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Neuropathology-based approach reveals novel Alzheimer's Disease genes and highlights female-specific pathways and causal links to disrupted lipid metabolism: insights into a vicious cycle.
Acta Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFGod Knows Best: Exploring the God Locus of Health Control, Race-Ethnicity, and Risk-Taking and Protective Behaviors Interrelationship in the USA.
J Relig Health
January 2025
Department of Sociology and Demography, The University of Texas at San Antoni, San Antonio, TX, USA.
The health implications of engaging in risk-taking or protective behaviors can have long-lasting effects on an individual's life. In recent years, there has been a growing interest in how religious attitudes and beliefs influence an individual's health behaviors. However, research on the role of the God Locus of Health Control (GLHC) in the religion-health literature is lacking.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Beth Israel Deaconess Medical Center, Boston, MA, USA.
Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.
Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Background: SNX19 is a key player in endolysosomal and autophagy pathways, which have been extensively reported in neuronal dysfunction and neurodegenerative diseases. Although genetic and cellular evidence suggests SNX19 contributes to neuropathology, the underlying mechanisms remain unknown. Here, we propose to study the mechanism in aging postmortem brain tissue at single cell level and model SNX19 in human induced pluripotent stem cell (hiPSCs) derived brain organoids.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Southern California, Los Angeles, CA, USA.
Background: Synaptic loss predicts cognitive decline in Alzheimer's disease (AD). However, the critical disease modifying molecular mechanisms of synaptic failure remain elusive. Animal studies implicate the increased activation of cytosolic phospholipase (cPLA2) activation in synaptic loss and neuroinflammation.
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