Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex

TY - JOUR

T1 - Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex

AU - Martín, Virginia

AU - Fabelo, Noemí

AU - Santpere, Gabriel

AU - Puig, Berta

AU - Marín, Raquel

AU - Ferrer, Isidre

AU - Díaz, Mario

AU - Puig Martorell, Berta

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

AB - Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

KW - Adenosine Triphosphatases

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Amyloid beta-Protein Precursor

KW - Analysis of Variance

KW - Caveolin 1

KW - Cerebral Cortex

KW - Clathrin

KW - Docosahexaenoic Acids

KW - Female

KW - Humans

KW - Lipids

KW - Male

KW - Membrane Microdomains

KW - Middle Aged

KW - Regression Analysis

KW - Superoxide Dismutase

KW - Young Adult

U2 - 10.3233/JAD-2010-1242

DO - 10.3233/JAD-2010-1242

M3 - SCORING: Journal article

C2 - 20110596

VL - 19

SP - 489

EP - 502

JO - J ALZHEIMERS DIS

JF - J ALZHEIMERS DIS

SN - 1387-2877

IS - 2

ER -