Skip to content
BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access December 6, 2013

Parahippocampal corpora amylacea and neuronal lipofuscin in human aging

Mirjana Bakić, Ivan Jovanović, Slađana Ugrenović, Ljiljana Vasović, Miljan Krstić, Natalija Stefanović, Miljana Pavlović and Vladimir Živković
From the journal Open Medicine


The aim of this research was to quantify the number of corpora amylacea and lipofuscin-bearing neurons in the parahippocampal region of the brain. Right parahippocampal gyrus specimens of 30 cadavers were used as material for histological and morphometric analyses. A combined Alcian Blue and Periodic Acid-Schiff technique was used for identification and quantification of corpora amylacea and lipofuscin-bearing neurons. Immunohistochemistry was performed using S100 polyclonal, neuron-specific enolase and glial fibrillary acidic protein monoclonal antibodies for differentiation of corpora amylacea and other spherical inclusions of the aging brain. Cluster analysis of obtained data showed the presence of three age groups (median age: I = 41.5, II = 68, III = 71.5). The second group was characterized by a significantly higher numerical density of subcortical corpora amylacea and number of lipofuscin-bearing neurons than other two groups. Values of the latter cited parameters in the third group were insignificantly higher than the first younger group. Linear regression showed that number of parahippocampal lipofuscin-bearing neurons significantly predicts numerical density of subcortical corpora amylacea. The above results suggest that more numerous parahippocampal region corpora amylacea and lipofuscin-bearing neurons in some older cases might represent signs of its’ neurons quantitatively-altered metabolism.

[1] Blaizot X., Martinez-Marcos A., Arroyo-Jimenez Md Mdel M., Marcos P., Artacho-Pérula E., Muñoz M., et al., The parahippocampal gyrus in the baboon: anatomical, cytoarchitectonic and magnetic resonance imaging (MRI) studies, Cereb. Cortex., 2004, 14, 231–246 in Google Scholar

[2] Van Hoesen GW., Anatomy of the medial temporal lobe Magn. Reson. Imaging., 1995, 13, 1047–1055 in Google Scholar

[3] Eichenbaum H., Lipton PA., Towards a functional organization of the medial temporal lobe memory system: role of the parahippocampal and medial entorhinal cortical areas, Hippocampus., 2008, 18, 1314–1324 in Google Scholar

[4] Keller JN., Age-related neuropathology, cognitive decline, and Alzheimer’s disease, Ageing. Res. Rev., 2006, 5, 1–13 in Google Scholar

[5] Tisserand DJ., Visser PJ., van Boxtel MP., Jolles J., The relation between global and limbic brain volumes on MRI and cognitive performance in healthy individuals across the age range, Neurobiol. Aging., 2000, 21, 569–576 in Google Scholar

[6] Du AT., Schuff N., Amend D., Laakso MP., Hsu YY., Jagust WJ., et al., Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease, J. Neurol. Neurosurg. Psychiatry., 2001, 71, 441–447 in Google Scholar

[7] Goncharova II., Dickerson BC., Stoub TR., deToledo-Morrell L., MRI of human entorhinal cortex: a reliable protocol for volumetric measurement. Neurobiol. Aging., 2001, 22, 737–745 in Google Scholar

[8] Bottino CM., Castro CC., Gomes RL., Buchpiguel CA., Marchetti RL., Neto MR., Volumetric MRI measurements can differentiate Alzheimer’s disease, mild cognitive impairment, and normal aging, Int. Psychogeriatr., 2002, 14, 59–72 in Google Scholar

[9] Pantel J., Kratz B., Essig M., Schröder J., Parahippocampal volume deficits in subjects with aging-associated cognitive decline, Am. J. Psychiatry., 2003, 160, 379–382 in Google Scholar

[10] Pennanen C., Kivipelto M., Tuomainen S., Hartikainen P., Hänninen T., Laakso MP., et al., Hippocampus and entorhinal cortex in mild cognitive impairment and early AD, Neurobiol. Aging., 2004, 25, 303–310 in Google Scholar

[11] Burgmans S., van Boxtel MP., van den Berg KE., Gronenschild EH., Jacobs HI., Jolles J., et al., The posterior parahippocampal gyrus is preferentially affected in age-related memory decline, Neurobiol. Aging., 2011, 32, 1572–1578 in Google Scholar

[12] Wang H., Golob E., Bert A., Nie K., Chu Y., Dick MB., et al., Alterations in regional brain volume and individual MRI-guided perfusion in normal control, stable mild cognitive impairment, and MCI-AD converter, J. Geriatr. Psychiatry. Neurol., 2009, 22, 35–45 in Google Scholar

[13] Sánchez-Benavides G., Gómez-Ansón B., Molinuevo JL., Blesa R., Monte GC., Buschke H., et al., Medial temporal lobe correlates of memory screening measures in normal aging, MCI, and AD. J. Geriatr. Psychiatry. Neurol., 2010, 23, 100–108 in Google Scholar

[14] Echávarri C., Aalten P., Uylings HB., Jacobs HI., Visser PJ., Gronenschild EH., et al., Atrophy in the parahippocampal gyrus as an early biomarker of Alzheimer’s disease, 2011, Brain. Struct. Funct., 2011, 215, 265–271 in Google Scholar

[15] Miettinen PS., Pihlajamäki M., Jauhiainen AM., Niskanen E., Hänninen T., Vanninen R., et al., Structure and function of medial temporal and posteromedial cortices in early Alzheimer’s disease, 2011, Eur. J. Neurosci., 34, 320–330 in Google Scholar

[16] Raz N., Gunning-Dixon FM., Head D., Dupuis JH., Acker JD., Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging, Neuropsychology., 1998, 12, 95–114 in Google Scholar

[17] Raz N., Rodrigue KM., Head D., Kennedy KM., Acker JD., Differential aging of the medial temporal lobe: a study of a five-year change, Neurology., 2004, 62, 433–438 in Google Scholar

[18] Raz N., Lindenberger U., Rodrigue KM., Kennedy KM., Head D., Williamson A., et al., Regional brain changes in aging healthy adults: general trends, individual differences and modifiers, Cereb. Cortex., 2005, 15, 1676–1689 in Google Scholar

[19] Raz N., Ghisletta P., Rodrigue KM., Kennedy KM., Lindenberger U., Trajectories of brain aging in middle-aged and older adults: regional and individual differences, Neuroimage., 2010, 51, 501–511 in Google Scholar

[20] Anderton BH., Ageing of the brain, Mech. Ageing. Dev., 2002, 123, 811–817 in Google Scholar

[21] Rapp PR., Deroche PS., Mao Y., Burwell RD., Neuron number in the parahippocampal region is preserved in aged rats with spatial learning deficits, Cereb. Cortex., 2002, 12, 1171–1179 in Google Scholar

[22] Heinsen H., Henn R., Eisenmenger W., Götz M., Bohl J., Bethke B., et al., Quantitative investigations on the human entorhinal area: left-right asymmetry and age-related changes, Anat. Embryol. (Berl)., 1994, 190, 181–194 10.1007/BF00193414Search in Google Scholar

[23] Gazzaley AH., Thakker MM., Hof PR., Morrison JH., Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys, Neurobiol. Aging., 1997, 18, 549–553 in Google Scholar

[24] Merrill DA., Roberts JA., Tuszynski MH., Conservation of neuron number and size in entorhinal cortex layers II, III, and V/VI of aged primates, J. Comp. Neurol., 2000, 422, 396–401<396::AID-CNE6>3.0.CO;2-R10.1002/1096-9861(20000703)422:3<396::AID-CNE6>3.0.CO;2-RSearch in Google Scholar

[25] Stranahan AM., Mattson MP., Selective vulnerability of neurons in layer II of the entorhinal cortex during aging and Alzheimer’s disease, Neural. Plast., 2010, 10.1155/2010/108190Search in Google Scholar

[26] Derflinger S., Sorg C., Gaser C., Myers N., Arsic M., Kurz A., et al., Grey-matter atrophy in Alzheimer’s disease is asymmetric but not lateralized, J. Alzheimers. Dis., 2011, 25, 347–357. 10.3233/JAD-2011-110041Search in Google Scholar

[27] Cavanagh JB., Corpora-amylacea and the family of polyglucosan diseases. Brain. Res. Brain. Res. Rev., 1999, 29, 265–295 in Google Scholar

[28] Kimura T., Takamatsu J., Miyata T., Miyakawa T., Horiuchi S., Localization of identified advanced glycation end-product structures, N epsilon(carboxymethyl)lysine and pentosidine, in age-related inclusions in human brains, Pathol. Int., 1998, 48, 575–579 in Google Scholar

[29] Singhrao SK., Neal JW., Piddlesden SJ., Newman GR., New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylacea, Neuropathol. Appl. Neurobiol., 1994, 20, 66–73 in Google Scholar

[30] Singhrao SK., Morgan BP., Neal JW., Newman GR., A functional role for corpora amylacea based on evidence from complement studies, Neurodegeneration., 1995, 4, 335–345 in Google Scholar

[31] Buervenich S., Olson L., Galter D., Nestin-like immunoreactivity of corpora amylacea in aged human brain, Brain. Res. Mol. Brain. Res., 2001, 94, 204–208 in Google Scholar

[32] Double KL., Dedov VN., Fedorow H., Kettle E., Halliday GM., Garner B., et al., The comparative biology of neuromelanin and lipofuscin in the human brain, Cell. Mol. Life. Sci., 2008, 65, 1669–1682 in Google Scholar

[33] Sulzer D., Mosharov E., Talloczy Z., Zucca FA., Simon JD., Zecca L., Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease, J. Neurochem., 2008, 106, 24–36 in Google Scholar

[34] Boellaard JW., Harzer K., Schlote W., Variations of the ultrastructure of neuronal lipofuscin during childhood and adolescence in the human Ammon’s horn, Ultrastruct. Pathol., 2006, 30, 387–391 in Google Scholar

[35] Russ J.C., Image analysis of food microstructure, 1st ed., CRC Press Taylor &Francis Group, Boca Raton Florida, 2004 in Google Scholar

[36] Kališnik M., Blejec A., Pajer Z., Majhenc J., Metric characteristics of various methods for numerical density estimation in transmission light microscopy — a computer simulation, 2001, Image. Anal. Stereol. 2001, 20, 15–25 in Google Scholar

[37] Leel-Ossy L., New data on the ultrastructure of the corpus amylaceum (polyglucosan body), Pathol. Oncol. Res., 2001, 7, 145–150 in Google Scholar

[38] Nishimura A., Sawada S., Ushiyama I., Yamamoto Y., Nakagawa T., Tanegashima A., et al., Lectinhistochemical detection of degenerative glycoconjugate deposits in human brain, Forensic. Sci. Int., 2000, 113 265–269 in Google Scholar

[39] Abel TJ., Hebb AO., Keene CD., Born DE., Silbergeld DL., Parahippocampal corpora amylacea: case report, Neurosurgery., 2010, 66, E1206–1207 in Google Scholar

[40] Selmaj K., Pawłowska Z., Walczak A., Koziołkiewicz W., Raine CS., Cierniewski CS., Corpora amylacea from multiple sclerosis brain tissue consists of aggregated neuronal cells. Acta. Biochim. Pol., 2008, 55, 43–49. 10.18388/abp.2008_3199Search in Google Scholar

[41] Hoyaux D., Decaestecker C., Heizmann CW., Vogl T., Schäfer BW., Salmon I., et al., S100 proteins in Corpora amylacea from normal human brain, Brain. Res., 2000, 867, 280–288 in Google Scholar

[42] Takahashi K., Iwata K., Nakamura H., Intra-axonal corpora amylacea in the CNS, Acta. Neuropathol., 1977, 37, 165–167 in Google Scholar

[43] Nishio S., Morioka T., Kawamura T., Fukui K., Nonaka H., Matsushima M., Corpora amylacea replace the hippocampal pyramidal cell layer in a patient with temporal lobe epilepsy, Epilepsia., 2001, 42, 960–962 in Google Scholar

[44] Gray DA., Woulfe J., Lipofuscin and aging: a matter of toxic waste, Sci. Aging. Knowledge. Environ., 2005, 10.1126/sageke.2005.5.re1Search in Google Scholar

[45] Riga D., Riga S., Halalau F., Schneider F., Brain lipopigment accumulation in normal and pathological aging, Ann. N. Y. Acad. Sci., 2006, 1067, 158–163 in Google Scholar

[46] Nakano M., Oenzil F., Mizuno T., Gotoh S., Agerelated changes in the lipofuscin accumulation of brain and heart, Gerontology., 1995, 41, 69–79 in Google Scholar

[47] Shimada A., Keino H., Kawamura N., Chiba Y., Hosokawa M., Limbic structures are prone to agerelated impairments in proteasome activity and neuronal ubiquitinated inclusions in SAMP10 mouse: a model of cerebral degeneration, Neuropathol. Appl. Neurobiol., 2008, 34, 33–51 10.1111/j.1365-2990.2007.00878.xSearch in Google Scholar

[48] Kimura T., Fujise N., Ono T., Shono M., Yuzuriha T., Katsuragi S., et al., Identification of an aging-related spherical inclusion in the human brain, Pathol. Int., 2002, 52, 636–642 in Google Scholar

[49] Raz N., Rodrigue KM., Differential aging of the brain: patterns, cognitive correlates and modifiers, Neurosci. Biobehav. Rev., 2006, 30, 730–748 in Google Scholar

Published Online: 2013-12-6
Published in Print: 2013-12-1

© 2013 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Scroll Up Arrow