Asian Journal of Physics  Vol. 31 No 2, 2022, 259-264

Raman and infrared microscopic study on the lipid redistribution in Alzheimer diseased murine tissue
Alicia Schirer, Youssef El Khoury, Christine Patte-Mensah, Christian Klein, Laurence Meyer, Monika Rataj-Baniowska, David Moss, Ayikoe-Guy Mensah-Nyagan Sophie Lecomte and Petra Hellwig


The Alzheimer disease (AD) is the most common form of dementia. Several stages characterize the neurodegenerative process from the early AD to severe AD. During these stages, major structural and molecular changes will spread throughout the cerebral cortex. Here, we present Raman and Infrared microscopic evidences for the reorganization of phospholipids in brain tissue from AD diseased tissues of mice with severe AD. On the basis of the imaging results, it can be shown that the lipid concentration around the aggregates increases and decreases in the plaques. In addition, a change of the ratio of unsaturated to saturated lipids is found pointing towards a changed metabolism. © Anita Publications. All rights reserved.
Keywords: Alzheimer disease; Raman microscopy, Infrared microscopy; Phospholipids; Aggregation Cascade.

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  1. LaFerla F M, Oddo S, Alzheimer’s disease: Aβ, tau and synaptic dysfunction. Trends Mol Med, 11(2005)170–176.
  2. Zhao Y, Zhao B, Oxidative stress and the pathogenesis of Alzheimer’s disease. Med. Cell. Longev, 2013(2013) 316523; /
  3. Svennerholm L, Bostrom K, Jungbjer B, Olsson L, Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years, J Neurochem, 63(1994)1802–1811.
  4. O’Brien J S, Sampson E L, Lipid composition of the normal human brain: gray matter, white matter, and myelin. J Lipid Res, 6(1965)537–544.
  5. Kishimoto Y, Agranoff B W, Radin N, Burton R M, Comparison of the fatty acids of lipids of subcellular brain fractions, J Neurochem, 16(1969)397–404.
  6. Torres M, Price S L, Fiol-Deroque M A, Marcilla-Etxenike A, Ahyayauch H, Barcelo-Coblijn G, Terés S, Katsouri L, Ordinas M, López D J, Ibarguren M, Goñi F M, Busquets X, Vitorica J, Sastre M, Escribá P V, Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimer’s disease, Biochim Biophys Acta, 1838(2014)1680–1692.
  7. Mohaibes R J, Fiol-deRoque M A, Torres M, Ordinas M, Lopez D J, Castro J A, Escribá P V, Busquets X, The hydroxylated form of docosahexaenoic acid (DHAH) modifies the brain lipid composition in a model of Alzheimer’s disease, improving behavioral motor function and survival, Biochim Biophys Acta Biomembr, 1859(2017)1596–1603.
  8. Nunan J, Small D H, Regulation of APP cleavage by alpha-, beta- and gamma-secretases, FEBS Lett, 483(2000) 6–10.
  9. Hartmann D, A brief history of APP secretases, their substrates and their functions, Curr Alzheimer Res, 9 (2012) 138–139.
  10. Ehehalt R, Keller P, Haass C, Thiele C, Simons K, Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts, J Cell Biol, 160(2003)113–123.
  11. Yoon I S, Chen E, Busse T, Repetto E, Lakshmana M K, Koo E H, Kang D E. Low-density lipoprotein receptor-related protein promotes amyloid precursor protein trafficking to lipid rafts in the endocytic pathway, FASEB J, 21(2007)2742–2752.
  12. Marquer C, Devauges V, Cossec J C, Liot G, Lecart S, Saudou F, Duyckaerts C, Leveque-Fort S, Potier M C Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis, FASEB J, 25(2011)1295–1305.
  13. Bhattacharyya R, Barren C, Kovacs D M Palmitoylation of amyloid precursor protein regulates amyloidogenic processing in lipid rafts, J Neurosci, 33(2013)11169–11183.
  14. Grimm M O, Rothhaar T L, Grosgen S, Burg V K, Hundsdorfer B, Haupenthal V J, Friess P, Kins S, Grimm H S, Hartmann T, Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (APP), J Nutr Biochem, 23(2012)1214–1223.
  15. Li M Z, Zheng L J, Shen J, Li X Y, Zhang Q, Bai X, Wang Q S, Ji J G. SIRT1 facilitates amyloid beta peptide degradation by upregulating lysosome number in primary astrocytes, Neural Regen Res, 13(2018)2005–2013.
  16. Grassi S, Giussani P, Mauri L, Prioni S, Sonnino S, Prinetti A, Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases, J Lipid Res, 61(2019)636–654.
  17. Kretlow A, Wang Q, Kneipp J, Lasch P, Beekes M, Miller L, Naumann D, FTIR-microspectroscopy of prion-infected nervous tissue, Biochim Biophys Acta, 1758(2006)948–959.
  18. Miller L M, Dumas P, Chemical imaging of biological tissue with synchrotron infrared light, Biochim Biophys, Acta, 1758(2006)846–857.
  19. Ooi G J, Fox J, Siu K, Lewis R, Bambery K R, McNaughton D, Wood B R, Fourier transform infrared imaging and small angle x-ray scattering as a combined biomolecular approach to diagnosis of breast cancer, Med Phys, 35(2008)2151–2161.
  20. El Khoury Y, Schirer A, Patte-Mensah C, Klein C, Meyer L, Rataj-Baniowska M, Bernad S, Moss D, Lecomte S, Mensah-Nyagan A G, Hellwig P, Raman Imaging Reveals Accumulation of Hemoproteins in Plaques from Alzheimer’s Diseased Tissues, ACS Chem Neurosci, 12(2021)2940–2945.
  21. Benseny-Cases N, Klementieva O, Cotte M, Ferrer I, Cladera J. Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains. Anal Chem, 86 (2014)12047–12054.
  22. Liao C R, Rak M, Lund J, Unger M, Platt E, Albensi B C, Hirschmugl C J, Gough K M, Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer’s disease brain, Analyst, 138(2013)3991–3997.
  23. Kiskis J, Fink H, Nyberg L, Thyr J, Li J Y, Enejder A, Plaque-associated lipids in Alzheimer’s diseased brain tissue visualized by nonlinear microscopy, Sci Rep, 5(2015)13489;
  24. Hsiao K, Chapman S, Nilsen P, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G, Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice, Science, 274(1996)99–102.
  25. Westerman M A, Cooper-Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin L H, Carlson G A, Younkin S G, Ashe K H, The Relationship between Aβ and Memory in the Tg2576 Mouse Model of Alzheimer’s Disease, J Neurosci, 22(2002)1858–1867.
  26. Mawuenyega K G, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris J C, Yarasheski K E, Bateman R J, Decreased clearance of CNS β-amyloid in Alzheimer’s disease, Science, 330(2010)1774; doi.10.1126/science.1197623.
  27. Ognibene E, Middei S, Daniele S, Adriani W, Ghirardi O, Caprioli A, Laviola G, APP transgenic mice for modelling behavioral and psychological symptoms of dementia (BPSD), Behav Brain Res, 156(2005)225–232.
  28. Yassine N, Lazaris A, Dorner-Ciossek C, Despres O, Meyer L, Maitre M, Mensah-Nyagan A G, Cassel J C, Mathis C, Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice, Neurobiol Aging, 34(2013)716–730.
  29. Barth A, Infrared spectroscopy of proteins, Biochim Biophys Acta, 1767(2007)1073–1101.
  30. Krimm S, Bandekar J, Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins, Adv Protein Chem, 38(1986)181–364.
  31. Chirgadze Y N, Nevskaya N A, Infrared spectra and resonance interaction of amide-I vibration of the antiparallel-chain pleated sheet, Biopolymers, 15(1976)607–625.
  32. Qiang W, Yau W M, Luo Y, Mattson M P, Tycko R, Structural Variation in Amyloid-β Fibrils from Alzheimer’s Disease Clinical Subtypes, Proc Natl Acad Sci (U S A), 109(2012) 4443–4448.
  33. Berthelot K, Ta H P, Gean J, Lecomte S, Cullin C, In vivo and in vitro analyses of toxic mutants of HET-s: FTIR antiparallel signature correlates with amyloid toxicity, J Mol Biol, 412(2011)137–152.