To examine the differences in the capacity to activate microglia in patients with Alzheimer's Disease (AD) compared to age-comparable cognitively normal subjects and younger healthy controls.
Name: LPSDescription: LPS (0.4 ng/kg)Type: Drug
Patients receiving endotoxin
Description: Th primary outcome is MARI (calculated in the parietal ROIs) in AD patients compared to elderly controls. The investigators will use 7 AD and 7 comparably aged cognitively normal successfully scanned subjects to calculate the microglial activation reserve index. It is expected that there will be significant differences between the two groups suggesting Altered reactivity of the microglia in AD.The result would be an exciting one suggesting at least one mechanism by which some patients with significant amyloid load have progressive dementia while comparable others are either cognitively normal or have stable MCI. It will also suggest avenues for intervention in amyloid positive MCIs to prevent progression to Alzheimer's dementiaMeasure: An altered reactivity of microglia Time: 180 minutes post intervention
Description: The investigators will evaluate the effects of aging on MARI. Comparisons will be made for MARI between cognitively normal elderly and the 8 healthy individual to whom the researchers applied this protocol in an earlier study. The reactivity of microglia is reported to change with age (11) and so MARI is expected to change in the cognitively normal elderly. However, it is expected that the differences between the young and elderly cognitively normal subjects to be small relative to the comparison of AD and elderly normal controls.Measure: Effects of aging on MARI Time: 180 minutes post intervention
Description: The investigators will look at the relationship of regional and global amyloid load to MARI. The presence of a relationship suggests that one of the reasons for altered microglial reactivity might be interactions of microglia with pathologic amyloid.Measure: Effects of amyloid on MARI Time: 180 minutes post intervention
Description: The investigators will explore whether MARI would correlate with measure of disease stage, with higher MARIs associated with worse neuropsychological score and more severe disease. The investigators will look for correlations between MARI and the individual neuropsychological scores. This would determine if disease severity is correlated with microglial activation reserve.Measure: Effects of MARI on cognition Time: 180 minutes post intervention
There is one SNP
- BMI > 35 or < 19 - Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or Intrauterine Device (IUD) - Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population) - Patients on antiplatelet and anticoagulant medications will be excluded.