Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease

Sachin Patil, Christina Chan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aâ) protein and intracellular accumulation of neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated. The hyperphosphorylation of tau disrupts the cytoskeleton, which leads to degeneration of affected neurons, thus playing an important role in AD pathology. Epidemiological studies suggest that high fat diet significantly increases the risk of AD and the degree of saturation of fatty acids is critical in determining the risk for AD. This is further supported by animal studies in which the mice fed high fat-high cholesterol diet developed AD-like pathophysiological changes in their brain. Despite these accumulating data the basic mechanism behind the causal relationship between fatty acids and the pathogenesis of AD has not been established. In this context, we show for the first time that saturated fatty acids (FFAs), palmitic and stearic acids, cause Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. The observed FFA-induced effect is mediated through astroglia-induced oxidative stress. How FFA metabolism in astrocytes results in the aforementioned effects in neurons is not clear. We are currently applying metabolic flux analysis (MFA) to gain some insight into the metabolic profiles of primary cortical astroglia and neuronal cultures in the presence of saturated FFAs. This may help to identify the metabolic pathways involved in the observed FFA-induced, AD-specific phenotypes in the neurons, as well as, novel targets related to FFA metabolism, for therapeutic intervention in AD.

Original languageEnglish (US)
Title of host publicationAIChE Annual Meeting, Conference Proceedings
Pages8964
Number of pages1
StatePublished - 2005
Externally publishedYes
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
CountryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

Profile

Neurons
Saturated fatty acids
Nutrition
Oils and fats
Fatty acids
Metabolism
Proteins
Neurodegenerative diseases
Palmitic acid
Stearic acid
Oxidative stress
Cholesterol
Pathology
Rats
Brain
Animals
Deposits
Fluxes

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Patil, S., & Chan, C. (2005). Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease. In AIChE Annual Meeting, Conference Proceedings (pp. 8964)

Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease. / Patil, Sachin; Chan, Christina.

AIChE Annual Meeting, Conference Proceedings. 2005. p. 8964.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Patil, S & Chan, C 2005, Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease. in AIChE Annual Meeting, Conference Proceedings. pp. 8964, 05AIChE: 2005 AIChE Annual Meeting and Fall Showcase, Cincinnati, OH, United States, 30-4 November.
Patil S, Chan C. Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease. In AIChE Annual Meeting, Conference Proceedings. 2005. p. 8964.

Patil, Sachin; Chan, Christina / Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease.

AIChE Annual Meeting, Conference Proceedings. 2005. p. 8964.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

@inbook{e0616326143241d9870a7ef821994b63,
title = "Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease",
abstract = "Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aâ) protein and intracellular accumulation of neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated. The hyperphosphorylation of tau disrupts the cytoskeleton, which leads to degeneration of affected neurons, thus playing an important role in AD pathology. Epidemiological studies suggest that high fat diet significantly increases the risk of AD and the degree of saturation of fatty acids is critical in determining the risk for AD. This is further supported by animal studies in which the mice fed high fat-high cholesterol diet developed AD-like pathophysiological changes in their brain. Despite these accumulating data the basic mechanism behind the causal relationship between fatty acids and the pathogenesis of AD has not been established. In this context, we show for the first time that saturated fatty acids (FFAs), palmitic and stearic acids, cause Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. The observed FFA-induced effect is mediated through astroglia-induced oxidative stress. How FFA metabolism in astrocytes results in the aforementioned effects in neurons is not clear. We are currently applying metabolic flux analysis (MFA) to gain some insight into the metabolic profiles of primary cortical astroglia and neuronal cultures in the presence of saturated FFAs. This may help to identify the metabolic pathways involved in the observed FFA-induced, AD-specific phenotypes in the neurons, as well as, novel targets related to FFA metabolism, for therapeutic intervention in AD.",
author = "Sachin Patil and Christina Chan",
year = "2005",
pages = "8964",
booktitle = "AIChE Annual Meeting, Conference Proceedings",

}

TY - CHAP

T1 - Involvement of saturated fatty acids in the pathogenesis of Alzheimer's disease

AU - Patil,Sachin

AU - Chan,Christina

PY - 2005

Y1 - 2005

N2 - Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aâ) protein and intracellular accumulation of neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated. The hyperphosphorylation of tau disrupts the cytoskeleton, which leads to degeneration of affected neurons, thus playing an important role in AD pathology. Epidemiological studies suggest that high fat diet significantly increases the risk of AD and the degree of saturation of fatty acids is critical in determining the risk for AD. This is further supported by animal studies in which the mice fed high fat-high cholesterol diet developed AD-like pathophysiological changes in their brain. Despite these accumulating data the basic mechanism behind the causal relationship between fatty acids and the pathogenesis of AD has not been established. In this context, we show for the first time that saturated fatty acids (FFAs), palmitic and stearic acids, cause Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. The observed FFA-induced effect is mediated through astroglia-induced oxidative stress. How FFA metabolism in astrocytes results in the aforementioned effects in neurons is not clear. We are currently applying metabolic flux analysis (MFA) to gain some insight into the metabolic profiles of primary cortical astroglia and neuronal cultures in the presence of saturated FFAs. This may help to identify the metabolic pathways involved in the observed FFA-induced, AD-specific phenotypes in the neurons, as well as, novel targets related to FFA metabolism, for therapeutic intervention in AD.

AB - Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aâ) protein and intracellular accumulation of neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated. The hyperphosphorylation of tau disrupts the cytoskeleton, which leads to degeneration of affected neurons, thus playing an important role in AD pathology. Epidemiological studies suggest that high fat diet significantly increases the risk of AD and the degree of saturation of fatty acids is critical in determining the risk for AD. This is further supported by animal studies in which the mice fed high fat-high cholesterol diet developed AD-like pathophysiological changes in their brain. Despite these accumulating data the basic mechanism behind the causal relationship between fatty acids and the pathogenesis of AD has not been established. In this context, we show for the first time that saturated fatty acids (FFAs), palmitic and stearic acids, cause Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. The observed FFA-induced effect is mediated through astroglia-induced oxidative stress. How FFA metabolism in astrocytes results in the aforementioned effects in neurons is not clear. We are currently applying metabolic flux analysis (MFA) to gain some insight into the metabolic profiles of primary cortical astroglia and neuronal cultures in the presence of saturated FFAs. This may help to identify the metabolic pathways involved in the observed FFA-induced, AD-specific phenotypes in the neurons, as well as, novel targets related to FFA metabolism, for therapeutic intervention in AD.

UR - http://www.scopus.com/inward/record.url?scp=33645646213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645646213&partnerID=8YFLogxK

M3 - Conference contribution

SP - 8964

BT - AIChE Annual Meeting, Conference Proceedings

ER -