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| http://dx.doi.org/10.1097/CM9.0000000000000139 | DOI Listing |
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Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most prevalent type of senile dementia affecting more than 6 million Americans in 2023. Most of these AD cases are sporadic or late-onset AD with unclear etiology. Recent clinical trials on antibody drug clearing Ab plagues in brain show modest benefits of slowing down cognitive decline.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: The Apoliproprotein E (APOE) e4 allele is the most significant genetic risk factor for late-onset Alzheimer disease (AD). However, the risk associated with the APOE e4 allele differs across populations with individuals of African ancestry having a reduced risk than individuals of European (EU) ancestry. Further, single-nuclei RNAseq analysis in autopsy samples from AD APOEε4 homozygotes with EU Local Ancestry (LA) had a significantly increased APOEε4 expression compared to those with African LA, particularly in astrocytes.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Background: Despite recent FDA approvement of disease-modifying treatments that reduce Aβ, the identification of novel therapeutic strategies that could delay the Alzheimer's disease (AD) development are needed. We identified and developed novel small molecule compounds that mildly inhibit mitochondrial complex I (MCI). Chronic treatment with a tool compound CP2 in 4 mouse models of familial AD was efficacious protecting against synaptic dysfunction and memory impairment, improving brain energetics and cognitive performance, reducing levels of human pTau and Ab.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Isakson Center for Neurological Disease Research, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Background: The Apolipoprotein-E (APOE) ε4 gene variant is the strongest genetic risk factor for late-onset Alzheimer's Disease, but is not entirely predictive. Emerging evidence suggests environmental factors contribute to disease etiology, with epidemiological studies associating pesticide exposure with lower cognitive scores. Dichlorodiphenyltrichloroethane (DDT), a pesticide used extensively in the US until 1972, persists in trace amounts due to its long half-life, bioaccumulation, and existing dumpsites.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Background: DNA microarray-based studies report differentially methylated positions (DMPs) in blood between cognitively unimpaired persons (CU) and persons with late-onset dementia due to Alzheimer's disease (AD) or Mild Cognitive Impairment (MCI) but interrogate less than 4% of the human genome. Whole genome methylation sequencing (WGMS) quantifies DNA methylation levels across the entire human genome (>25 million CpG loci). Using WGMS, we previously reported 28,038 DMPs within 2,707 genes between persons with and without AD.
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