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Lipids in Alzheimer’s Disease Brain

  • Reference work entry
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Lipids are important biological molecules. The lipids of physiological importance for humans have four major functions: (1) structural components of biological membranes; (2) energy reserves, predominantly in the form of triacylglycerols; (3) both lipids and lipid derivatives serve as vitamins and hormones, and (4) lipophilic bile acids aid in lipid solubilization. Fatty acids fill two major roles in the body: as the components of more complex membrane lipids and as the major components of stored fat in the form of triacylglycerols. Alterations in lipid structure and/or metabolism lead to many neurodegenerative diseases, among which Alzheimer’s disease (AD) is of great concern due to the increasing life-span of the world’s population. Additionally, altered cholesterol metabolism, modulation in phospholipid content, and phospholipid asymmetry in plasma membranes may play pivotal role in the progression of AD. Amyloid β-peptide [Aβ (1–42)] plays a central role in the pathogenesis of AD. Aβ (1–42) is heavily deposited in the brains of Alzheimer’s disease (AD) patients, and free radical oxidative stress of neuronal lipids is extensive. Research by our group and others suggests that this observation is linked to Aβ-induced oxidative stress in AD brain. This chapter summarizes current knowledge on lipid alterations in AD brain, one potential cause of the external oxidative stress in AD brain, and the consequences of Aβ-induced lipid peroxidation in this neurodegenerative disorder.

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Abbreviations

AD:

Alzheimer’s disease

Aβ(1-42):

amyloid beta-peptide

PtdSer:

Phosphatidylserine

PtdEtn:

Phosphatidylethanolamine

PtdIns:

phosphatidylinositol

PtdCho:

phosphatidylcholine

GEM:

glycosphingolipid-enriched membranes

RBC:

red blood cells

i-NOS:

inducible nitric oxide synthase

GPC:

glycerophosphatidylcholine

GPE:

glycerophosphatidylethanolamine

sPLA2 :

Ca2+ -dependent secretory phospholipase A2;  cPLA2, Ca2+ -dependent cytosolic phospholipase A2

iPLA2 :

Ca2+ -independent phospholipase A2

HNE:

4-hydroxy-2-nonenal

DAG:

diacylglycerol

NCT:

nicastrin

βaPP:

β-amyloid precursor protein

TBARS:

thiobarbituric acid reactive substances

IsoPs:

isoprostanes

NPs:

neuroprostanes

PG:

prostaglandin

LV:

levuglandins

NeuroKs:

neuroketals

NFT:

neurofibrillary tangles

SP:

senile plaques

FAEE:

ferulic acid ethyl ester

MCL:

mild cognitive impairment

ROS:

reactive oxygen species

RNS:

reactive nitrogen species

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Acknowledgment

This work was supported, in part, by NIH (NIA) grants to D. A. B.

Authors
  1. D. A. Butterfield
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  2. H. M. Abdul
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Medical Chemistry, Biochemistry and Biotechnology, Via Saldini 50, 20133, Milan, Italy

    Guido Tettamanti

  3. Department of Internal Medicine Section of Biochemistry, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Gianfrancesco Goracci

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Butterfield, D.A., Abdul, H.M. (2009). Lipids in Alzheimer’s Disease Brain. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_22

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