Peripheral amyloid-beta levels regulate amyloid-beta clearance from the central nervous system.

Amyloid-beta (Abeta) is cleared from the brain by both proteolytic digestion and transport across the blood-brain-barrier into the peripheral circulatory system. To investigate the role peripheral Abeta levels play in regulating Abeta brain clearance, we measured the clearance of [125I]-Abeta(1-40) injected into the brains of liver-ligated rats that allowed peripheral Abeta levels to be maintained at elevated levels for approximately one hour with/without a single peripheral bolus of unlabeled Abeta(1-40). We found that elevating peripheral Abetalevels significantly decreased [125I]-Abeta(1-40) brain clearance, thus supporting the hypothesis that peripheral Abeta levels regulate Abeta clearance from the central nervous system.

Combined statin and niacin therapy remodels the high-density lipoprotein proteome.

Background: Boosting low high-density lipoprotein (HDL) levels is a current strategy for preventing clinical events that result from cardiovascular disease. We previously showed that HDL(3) of subjects with coronary artery disease is enriched in apolipoprotein E and that the lipoprotein carries a distinct protein cargo. This observation suggests that altered protein composition might affect the antiatherogenic and antiinflammatory properties of HDL.

Differential modulation of plasma beta-amyloid by insulin in patients with Alzheimer disease.

Background: Hyperinsulinemia and insulin resistance are risk factors for memory impairment and Alzheimer disease (AD). Insulin regulates levels of the amyloid beta-peptide (Abeta) in vitro in neuronal cultures and in vivo in the CSF of normal older adults.

Objective: To determine whether insulin affected plasma Abeta levels and whether such effects differed for patients with AD compared with normal older adults.

Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice.

The thiazolidinediones, such as rosiglitazone, increase peripheral insulin sensitivity and their use is proposed for the treatment of Alzheimer's disease. However, the mechanisms underlying the potential beneficial effects of rosiglitazone in Alzheimer's disease remain unclear. In previous studies, we observed that Tg2576 Alzheimer mice develop peripheral insulin resistance with age and have much higher serum corticosterone levels than wild-type mice when fasted overnight.

Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study.

Objective: Insulin resistance (impaired insulin action) has been associated with Alzheimer disease (AD) and memory impairment, independent of AD. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists improve insulin sensitivity and regulate in-vitro processing of the amyloid precursor protein (APP). Authors evaluated the effects of the PPAR-gamma agonist rosiglitazone on cognition and plasma levels of the APP derivative beta-amyloid (Abeta) in humans.