BACKGROUND: Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer's disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 2...
The role of microglia in the amyloid cascade of Alzheimer's disease (AD) is debated due to conflicting findings. Using a genetic and a pharmacological approach we demonstrate that depletion of microglia before amyloid-β (Aβ) plaque deposition, leads to a reduction in plaque numbers and neuritic dystrophy, confirming their role in plaque initiation....
IntroductionAlzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups.MethodsTwo cortical regions, from multiple centers, were har...
BACKGROUND: Alzheimer's disease (AD) brains commonly exhibit various co-morbid pathologies, with cerebral amyloid angiopathy (CAA) being the most prevalent, affecting 70-90% of patients. CAA can be restricted to medium and large vessels or extend to capillaries. Additionally, AD patients often show pathologies involving phosphorylated-TDP-43 (pTDP-...
The early initiation of binge-drinking and biological sex are critical risk factors for the development of affective disturbances and cognitive decline, as well as neurodegenerative diseases including Alzheimers disease. Further, a history of excessive alcohol consumption alters normal age-related changes in the pattern of protein expression in the...
The amyloid beta (Aβ) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aβ peptides could also represent relevant biomarkers. We measured levels of Aβ38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aβ levels and amyloid positron-emission-tomogr...
BackgroundIndividuals with Down syndrome (DS) are at high risk of early-onset Alzheimer's disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21....
BackgroundMicroglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding proc...
IntroductionSubjective cognitive decline (SCD) may be an early marker of Alzheimer's disease (AD) pathology. Until recently, it was impossible to measure biomarkers specific for α-synuclein pathology; therefore, its association with subjective reports of cognitive decline is unknown.MethodsAlzheimer's Disease Neuroimaging Initiative participants wi...
BackgroundChronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with Alzheimer's disease (AD)-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation.MethodsParticipants were men without dementia. Chronic pain...
