Skip to main content
Log in

Decreases in Phospholipids Containing Adrenic and Arachidonic Acids Occur in the Human Hippocampus over the Adult Lifespan

  • Original Article
  • Published:
Lipids

Abstract

One of the biggest risk factors for developing Alzheimer’s disease is advanced age. Despite several studies examining changes to phospholipids in the hippocampus during the pathogenesis of Alzheimer’s disease, little is known regarding changes to phospholipids in this region during normal adult aging. This study examined the phospholipid composition of the mitochondrial and microsomal membranes of the human hippocampus from post-mortem tissue of neurologically normal subjects aged between 18 and 104 years. Many of the age-related changes found were in low-to-moderately abundant phospholipids in both membrane fractions, with decreases with age being seen in many phospholipids containing either adrenic or arachidonic acid. The most abundant phospholipid of this type was phosphatidylethanolamine 18:0_22:4, which decreased in both the mitochondrial and microsomal membranes by approximately 20 % from ages 20 to 100. Subsequent decreases with age were seen in total adrenic and arachidonic acid in the phospholipids of both membrane fractions, but not in either fatty acid specifically within the phosphatidylethanolamine class. Increases with age were seen in the hippocampus for mitochondrial phosphatidylserine 18:0_22:6. This is the first report of changes to molecular phospholipids of the human hippocampus over the adult lifespan, with this study also providing a comprehensive profile of the phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine phospholipids of the human hippocampus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

ARA:

Arachidonic acid

DHA:

Docosahexaenoic acid

ChoGpl:

Choline glycerophospholipids

EtnGpl:

Ethanolamine glycerophospholipids

PakCho:

Plasmanyl phosphatidylcholine

PakEtn:

Plasmanyl phosphatidylethanolamine

PlsEtn:

Plasmenyl phosphatidylethanolamine (ethanolamine plasmalogen)

PtdCho:

Phosphatidylcholine

PtdEtn:

Phosphatidylethanolamine

PtdSer:

Phosphatidylserine

PUFA:

Polyunsaturated fatty acid(s)

References

  1. WHO, Alzheimer’s Disease International (2012) Dementia: a public health priority. In: WHO. http://www.who.int/mental_health/publications/dementia_report_2012/en/. Accessed 12 Feb 2014

  2. Kosicek M, Hecimovic S (2013) Phospholipids and Alzheimer’s disease: alterations, mechanisms and potential biomarkers. Int J Mol Sci 14:1310–1322. doi:10.3390/ijms14011310

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Mapstone M, Cheema AK, Fiandaca MS et al. (2014) Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med 20:415–418. doi:10.1038/nm.3466

    Article  CAS  PubMed  Google Scholar 

  4. Fox NC, Crum WR, Scahill RI et al (2001) Imaging of onset and progression of Alzheimer’s disease with voxel-compression mapping of serial magnetic resonance images. The Lancet 358:201–205. doi:10.1016/S0140-6736(01)05408-3

    Article  CAS  Google Scholar 

  5. Scahill RI, Schott JM, Stevens JM et al (2002) Mapping the evolution of regional atrophy in Alzheimer’s disease: unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci 99:4703–4707. doi:10.1073/pnas.052587399

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Scahill RI, Frost C, Jenkins R et al (2003) A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol 60:989–994. doi:10.1001/archneur.60.7.989

    Article  PubMed  Google Scholar 

  7. Ewers M, Insel P, Jagust WJ et al. (2012) CSF biomarker and PIB-PET–derived beta-amyloid signature predicts metabolic, gray matter, and cognitive changes in nondemented subjects. Cereb Cortex 22:1993–2004. doi:10.1093/cercor/bhr271

    Article  PubMed Central  PubMed  Google Scholar 

  8. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol Berl 82:239–259

    Article  CAS  PubMed  Google Scholar 

  9. Corrigan FM, Horrobin DF, Skinner ER et al (1998) Abnormal content of n-6 and n-3 long-chain unsaturated fatty acids in the phosphoglycerides and cholesterol esters of parahippocampal cortex from Alzheimer’s disease patients and its relationship to acetyl CoA content. Int J Biochem Cell Biol 30:197–207

    Article  CAS  PubMed  Google Scholar 

  10. Guan Z, Wang Y, Cairns NJ et al (1999) Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with Alzheimer disease. J Neuropathol Exp Neurol 58:740–747

    Article  CAS  PubMed  Google Scholar 

  11. Prasad MR, Lovell MA, Yatin M et al (1998) Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 23:81–88

    Article  CAS  PubMed  Google Scholar 

  12. Skinner ER, Watt C, Besson JAO, Best PV (1993) Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer’s disease and control subjects. Brain 116:717–725. doi:10.1093/brain/116.3.717

    Article  PubMed  Google Scholar 

  13. Söderberg M, Edlund C, Alafuzoff I et al (1992) Lipid composition in different regions of the brain in Alzheimer’s disease/senile dementia of Alzheimer’s type. J Neurochem 59:1646–1653

    Article  PubMed  Google Scholar 

  14. Wells K, Farooqui AA, Liss L, Horrocks LA (1995) Neural membrane phospholipids in Alzheimer disease. Neurochem Res 20:1329–1333. doi:10.1007/BF00992508

    Article  CAS  PubMed  Google Scholar 

  15. Söderberg M, Edlund C, Kristensson K, Dallner G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26:421–425

    Article  PubMed  Google Scholar 

  16. Söderberg M, Edlund C, Kristensson K, Dallner G (1990) Lipid compositions of different regions of the human brain during aging. J Neurochem 54:415–423

    Article  PubMed  Google Scholar 

  17. O’Brien JS, Sampson EL (1965) Lipid composition of the normal human brain: gray matter, white matter, and myelin. J Lipid Res 6:537–544

    PubMed  Google Scholar 

  18. Yetukuri L, Ekroos K, Vidal-Puig A, Orešič M (2008) Informatics and computational strategies for the study of lipids. Mol BioSyst 4:121–127. doi:10.1039/B715468B

    Article  CAS  PubMed  Google Scholar 

  19. Svennerholm L (1968) Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res 9:570–579

    CAS  PubMed  Google Scholar 

  20. Martínez M, Mougan I (1998) Fatty acid composition of human brain phospholipids during normal development. J Neurochem 71:2528–2533. doi:10.1046/j.1471-4159.1998.71062528.x

    Article  PubMed  Google Scholar 

  21. Blanksby SJ, Mitchell TW (2010) Advances in mass spectrometry for lipidomics. Annu Rev Anal Chem Palo Alto Calif 3:433–465. doi:10.1146/annurev.anchem.111808.073705

    Article  CAS  PubMed  Google Scholar 

  22. Norris SE, Friedrich MG, Mitchell TW et al (2015) Human prefrontal cortex phospholipids containing docosahexaenoic acid increase during normal adult aging, whereas those containing arachidonic acid decrease. Neurobiol Aging 36:1659–1669. doi:10.1016/j.neurobiolaging.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  23. Liebisch G, Vizcaíno JA, Köfeler H et al (2013) Shorthand notation for lipid structures derived from mass spectrometry. J Lipid Res 54:1523–1530. doi:10.1194/jlr.M033506

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Sprecher H (2000) Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta BBA Mol Cell Biol Lipids 1486:219–231. doi:10.1016/S1388-1981(00)00077-9

    Article  CAS  Google Scholar 

  25. Brooksbank BW, Martinez M (1989) Lipid abnormalities in the brain in adult Down’s syndrome and Alzheimer’s disease. Mol Chem Neuropathol Spons Int Soc Neurochem World Fed Neurol Res Groups Neurochem Cerebrospinal Fluid 11:157–185

    CAS  Google Scholar 

  26. Fraser T, Tayler H, Love S (2010) Fatty acid composition of frontal, temporal and parietal neocortex in the normal human brain and in Alzheimer’s disease. Neurochem Res 35:503–513. doi:10.1007/s11064-009-0087-5

    Article  CAS  PubMed  Google Scholar 

  27. Baylis D, Bartlett DB, Patel HP, Roberts HC (2013) Understanding how we age: insights into inflammaging. Longev Heal 2:8. doi:10.1186/2046-2395-2-8

    Article  Google Scholar 

  28. Kim H-Y, Akbar M, Kim Y-S (2010) Phosphatidylserine-dependent neuroprotective signaling promoted by docosahexaenoic acid. Prostaglandins Leukot Essent Fat Acids PLEFA 82:165–172. doi:10.1016/j.plefa.2010.02.025

    Article  CAS  Google Scholar 

  29. Martinez M (1992) Abnormal profiles of polyunsaturated fatty acids in the brain, liver, kidney and retina of patients with peroxisomal disorders. Brain Res 583:171–182. doi:10.1016/S0006-8993(10)80021-6

    Article  CAS  PubMed  Google Scholar 

  30. Hassan-Zadeh E, Baykal-Caglar E, Alwarawrah M, Huang J (2014) Complex roles of hybrid lipids in the composition, order, and size of lipid membrane domains. Langmuir 30:1361–1369. doi:10.1021/la4044733

    Article  CAS  PubMed  Google Scholar 

  31. Klose C, Surma MA, Simons K (2013) Organellar lipidomics—background and perspectives. Curr Opin Cell Biol 25:406–413. doi:10.1016/j.ceb.2013.03.005

    Article  CAS  PubMed  Google Scholar 

  32. Szekely O, Schilt Y, Steiner A, Raviv U (2011) Regulating the size and stabilization of lipid raft-like domains and using calcium ions as their probe. Langmuir 27:14767–14775. doi:10.1021/la203074q

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge technical assistance with tissue preparation from Dr. Surabhi Bhatia, Mrs. Kalani Ruberu, Dr. Sarah Abbott and Mrs. Amanda Skora. Human brain tissue was received from the New South Wales Tissue Resource Centre at the University of Sydney, which is supported by the National Health and Medical Research Council of Australia, Schizophrenia Research Institute and the National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725). The present research was supported by a grant from the National Health and Medical Research Council of Australia (1008667). TWM is supported by an ARC Future Fellowship (FT110100249).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah E. Hancock.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1262 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hancock, S.E., Friedrich, M.G., Mitchell, T.W. et al. Decreases in Phospholipids Containing Adrenic and Arachidonic Acids Occur in the Human Hippocampus over the Adult Lifespan. Lipids 50, 861–872 (2015). https://doi.org/10.1007/s11745-015-4030-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-015-4030-z

Keywords

Navigation