Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease.

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3 × Tg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3:n-6 PUFA ratio upward in the brain (+11%, p < 0.

High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model.

To investigate potential dietary risk factors of Alzheimer's disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice.

Decreased drebrin mRNA expression in Alzheimer disease: correlation with tau pathology.

To investigate the mRNA expression of the dendritic spine protein drebrin in Alzheimer's disease (AD), we performed post-mortem in situ hybridization studies in brain sections from 20 AD patients and 21 controls. AD diagnosis was confirmed by decreased drebrin protein and increased Abeta(40) (+464%; P < 0.05), Abeta(42) (+369%; P < 0.

Biochemical characterization of Abeta and tau pathologies in mild cognitive impairment and Alzheimer's disease.

We report a post mortem biochemical analysis of amyloid-beta (Abeta) (ELISA) and tau (Western immunoblots) in the temporo-parietal neocortex of subjects with a clinical diagnosis of mild cognitive impairment (MCI, n=12), Alzheimer's disease (AD, n=12) or no cognitive impairment (NCI, n=12). Levels of Abeta _{42} in the detergent-insoluble protein fractions were significantly higher in persons with AD but did not differentiate individuals with MCI. Conversion of tau into its insoluble form (soluble/insoluble tau ratio) or into paired helical filament tau (PHF_{tau}) were the biochemical variables most closely related to clinical and neuropathological diagnoses, but they did not distinguished MCI from the two other groups.

Novel liposomal formulation for targeted gene delivery.

Purpose: Development of a polyethylene glycol (PEG)-stabilized immunoliposome (PSIL) formulation with high DNA content suitable for in vivo intravenous administration and targeted gene delivery.

Materials And Methods: Plasmid DNA was condensed using 40% ethanol and packaged into neutral PSILs targeted to the mouse transferrin receptor using monoclonal antibodies (MAbs; clones RI7 and 8D3) attached to their PEG maleimide moieties. PSILs size was measured by quasi-elastic light scattering.