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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide. Dysregulation of various metabolism pathways may mediate the development of AD pathology and cognitive dysfunction. Variants of triggering receptor expressed on myeloid cells-2 (TREM2) are known to increase the risk of developing AD.
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Alzheimers Dement
December 2024
Nagoya City University, Nagoya, Japan.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and a leading cause of senile dementia. Accumulation of amyloid-β (Aβ) in the brains causes chronic neuroinflammation, synaptic loss, and neurovascular damage, which is thought to initiate decades-long AD pathogenesis. Recent clinical trials for anti-Aβ immunotherapy highlights the utility of biomarkers that faithfully reflect Aβ-related brain pathology to diagnose AD at the preclinical stage, to predict the onset and progression of the disease, and to assess the therapeutic efficacy of drugs.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, Columbia University, New York, NY, USA.
Background: At least one-third of the identified risk alleles from Genome Wide Association Studies of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. BIN1 which is also known as Amphiphysin 2; and PICALM which are involved in phosphoinositide metabolism and binding rank just below the highest risk gene variant of Apolipoprotein E (ApoEε4), a cholesterol and phospholipid transporter. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, CSF, blood and multiple mouse models of AD.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The Jackson Laboratory, Bar Harbor, ME, USA.
Background: Altered lipid profiles and lipid processing genes are associated with Alzheimer's disease (AD). There is a reported genetic interaction between the AD risk gene APOE and cholesterol ester transfer protein (CETP). Mice lack functional CETP which is critical to the balance of circulating lipoproteins; this imparts cardioprotective effects and may make mice resistant to AD.
View Article and Find Full Text PDFBackground: Bile acids (BA) are steroids regulating nutrient absorption, energy metabolism, and mitochondrial function, and serve as important signaling molecules with a role in the gut-brain axis. The composition of BAs in humans changes with diet type and health status, which is well documented with a few known bile acids. In this study, we leveraged a new BA-specific spectral library curated in the Dorrestein lab at UCSD to expand the pool of detected BAs in Alzheimer-related LC-MS/MS datasets and provide links to dietary profiles and AD markers.
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