Long-term Impact of Weight Loss Intervention on Changes in Cognitive Function: Exploratory Analyses from the Action for Health in Diabetes Randomized Controlled Clinical Trial.

Background: Diabetes adversely impacts cognition. Lifestyle change can improve diabetes control and potentially improve cognition. We examined whether weight loss through reduced caloric intake and increased physical activity was associated with slower cognitive aging in older adults with type 2 diabetes mellitus.

Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease.

Alzheimer's disease is a multifactorial, progressive, age-related neurodegenerative disease. In familial Alzheimer's disease, Abeta is excessively produced and deposited because of mutations in the amyloid precursor protein, presenilin-1, and presenilin-2 genes. Here, we generated a double homozygous knock-in mouse model that incorporates the Swedish familial Alzheimer's disease mutations and converts mouse Abeta to the human sequence in amyloid precursor protein and had the P264L familial Alzheimer's disease mutation in presenilin-1.

Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease.

Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cognitive function and early dementia or clinically probable Alzheimer's disease (AD). Oxidative stress plays a significant role in AD and is increased in the superior/middle temporal gyri of MCI subjects. Because AD involves hippocampal-resident memory dysfunction, we determined protein oxidation and identified the oxidized proteins in the hippocampi of MCI subjects.

Proteasome or calpain inhibition does not alter cellular tau levels in neuroblastoma cells or primary neurons.

Impaired tau catabolism may contribute to tau accumulation and aggregation in Alzheimer's disease and neurofibrillary tangle formation. This study examined the effects of proteasome and calpain inhibition on tau levels and turnover in primary rat hippocampal neurons and differentiated SH-SY5Y human neuroblastoma cells. Administration of proteasome (MG-115, lactacystin) or calpain (MDL28170) inhibitors for up to 24 hours did not alter tau levels in differentiated SH-SY5Y cells or rat hippocampal neurons.

Protective effect of the xanthate, D609, on Alzheimer's amyloid beta-peptide (1-42)-induced oxidative stress in primary neuronal cells.

Tricyclodecan-9-yl-xanthogenate (D609) is an inhibitor of phosphatidylcholine-specific phospholipase C, and this agent also has been reported to protect rodents against oxidative damage induced by ionizing radiation. Previously, we showed that D609 mimics glutathione (GSH) functions and that a disulfide is formed upon oxidation of D609 and the resulting dixanthate is a substrate for GSH reductase, regenerating D609. Considerable attention has been focused on increasing the intracellular GSH levels in many diseases, including Alzheimer's disease (AD).

Intrinsic differences in brain and spinal cord mitochondria: Implication for therapeutic interventions.

It is well known that regions of the CNS differentially respond to insults. After brain injury, cyclosporine A reduces damage but is ineffective following spinal cord injury. We address this disparity by assessing several parameters of mitochondrial physiology in the normal neocortex and spinal cord.