Article

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

Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
Neurobiology of aging (Impact Factor: 4.85). 11/2008; 31(9):1516-31. DOI: 10.1016/j.neurobiolaging.2008.08.022
Source: PubMed

ABSTRACT 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. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.

1 Follower
 · 
194 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interactions between apolipoprotein E (apo E) and amyloid beta (Aβ) are associated with the peripheral clearance of Aβ and are important to the development of neurodegenerative diseases. Interests in acute phase proteins (APP) as biomarkers for the early progression of Alzheimer's disease indicate that the peripheral Aβ metabolism is perturbed and the role of nutritional diets are important to reduce APPs to maintain peripheral Aβ clearance with relevance to hepatic cholesterol homeostasis and brain amyloidosis. The role of nutriproteomic diets that reverse the effects of high fat diets are associated with the reduction in APPs, cholesterol homeostasis and improved clearance of Aβ. Nutritional diets that reduce the increase in plasma endotoxins (gut microbiotica) such as lipopolysaccarides (LPS) reduce the effects of LPS on cell membranes and increase the cellular uptake of Aβ by interactions with apo E. LPS alter hepatic lipid metabolism with an increase hepatic cytokines and APPs in plasma. Interactions between apo E and Aβ are altered by LPS with increased binding of LPS to apo E with effects on electrostatic alterations in Aβ oligomers. The role of LPS in neurodegenerative diseases includes the effects of LPS on alpha-synuclein metabolism with relevance to Parkinson's disease and Alzheimer's disease.
    Advances in Aging Research 03/2015; 4(2):69-77. DOI:10.4236/aar.2015.42009
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In mammals, the central nervous system (CNS) is the most cholesterol rich organ by weight. Cholesterol metabolism is tightly regulated in the CNS and all cholesterol available is synthesized in situ. Deficits in cholesterol homeostasis at the level of synthesis, transport, or catabolism result in severe disorders featured by neurological disability. Recent studies indicate that a disturbed cholesterol metabolism is involved in CNS disorders, such as Alzheimer’s disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In contrast to circulating cholesterol, dietary plant sterols, can cross the blood-brain barrier and accumulate in the membranes of CNS cells. Plant sterols are well-known for their ability to lower circulating cholesterol levels. The finding that they gain access to the CNS has fueled research focusing on the physiological roles of plant sterols in the healthy and diseased CNS. To date, both beneficial and detrimental effects of plant sterols on CNS disorders are defined. In this review, we discuss recent findings regarding the impact of plant sterols on homeostatic and pathogenic processes in the CNS, and elaborate on the therapeutic potential of plant sterols in CNS disorders. doi 10.1016/j.plipres.2015.01.003
    Progress in Lipid Research 01/2015; 58. DOI:10.1016/j.plipres.2015.01.003 · 12.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer's disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer's disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones.
    Cellular and Molecular Life Sciences CMLS 02/2015; DOI:10.1007/s00018-015-1839-9 · 5.86 Impact Factor

Full-text

Download
116 Downloads
Available from
May 29, 2014