Morphologic features of synaptic structures associated with human cortical amyloid plaques

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Abstract

BACKGROUND: Progressive and irreversible synaptic loss is a key manifestation of Alzheimer’s disease (AD) that correlates with the degree of AD-associated cognitive impairment. The study of synaptic impairment may be necessary to understand the AD development and progression. Therefore, it seems important to analyze structural and functional changes in synapses during the development of this disease. Synaptophysin, a synaptic vesicle membrane protein, is one of the most reliable and widely used synaptic markers in such studies.

AIM: The aim of this study was to investigate the morphological characteristics of synaptophysin-containing structures in the human cerebral cortex during amyloid plaque formation.

MATERIALS AND METHODS: The study used cerebral cortex samples (n = 10) from men and women between the ages of 65 and 94 years. A new and original technique for light microscopy based on immunohistochemical detection of synaptophysin and staining of amyloid plaques with Alcian Blue was used for the simultaneous detection of synapses and amyloid plaques.

RESULTS: In most amyloid plaques, abnormal synaptophysin-immunopositive structures were found, presumably representing dystrophic presynapses. These structures were characterized by large size and diffuse shape and were found exclusively in amyloid plaques. It should be mentioned that polysaccharide bodies (corpora amylacea) were detected in all samples of the cerebral cortex, characterized by a distinct spherical shape and located predominantly near the meninges, periventricularly and perivascularly. Synaptophysin-immunopositive terminals surrounding polysaccharide bodies had a typical structure and distribution density in all cases and showed no signs of abnormality.

CONCLUSIONS: In the cerebral cortex of elderly, senile, and long-lived individuals with AD, abnormal synaptophysin-containing structures form within or around amyloid plaques. Further study of these structures promises to identify new biomarkers of synaptic disorganization, including AD and early diagnostic markers for AD.

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About the authors

Valeria V. Guselnikova

Institute of Experimental Medicine

Author for correspondence.
Email: Guselnicova.Valeriia@yandex.ru
ORCID iD: 0000-0002-9499-8275
SPIN-code: 5115-4320

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Valeria A. Razenkova

Institute of Experimental Medicine

Email: valeriya.raz@yandex.ru
ORCID iD: 0000-0002-3997-2232
SPIN-code: 8877-8902
Russian Federation, Saint Petersburg

Elena A. Fedorova

Institute of Experimental Medicine

Email: el-fedorova2014@ya.ru
ORCID iD: 0000-0002-0190-885X
SPIN-code: 5414-4122

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Dmitry E. Korzhevsky

Institute of Experimental Medicine

Email: dek2@yandex.ru
ORCID iD: 0000-0002-2456-8165
SPIN-code: 3252-3029

MD, Dr. Sci. (Medicine), Professor of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

References

  1. Meftah S, Gan J. Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Front Synaptic Neurosci. 2023;15:1129036. doi: 10.3389/fnsyn.2023.1129036
  2. Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–1590. doi: 10.1016/S0140-6736(20)32205-4
  3. Condello C, Schain A, Grutzendler J. Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition. Sci Rep. 2011;1:19. doi: 10.1038/srep00019
  4. Colom-Cadena M, Spires-Jones T, Zetterberg H, et al. The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease. Alzheimers Res Ther. 2020;12(1):21. doi: 10.1186/s13195-020-00588-4
  5. Peng L, Bestard-Lorigados I, Song W. The synapse as a treatment avenue for Alzheimer’s disease. Mol Psychiatry. 2022;27(7):2940–2949. doi: 10.1038/s41380-022-01565-z
  6. Lacor PN, Buniel MC, Furlow PW, et al. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J Neurosci. 2007;27:796–807. doi: 10.1523/JNEUROSCI.3501-06.2007
  7. Subramanian J, Savage JC, Tremblay MÈ. Synaptic loss in Alzheimer’s disease: mechanistic insights provided by two-photon in vivo imaging of transgenic mouse models. Front Cell Neurosci. 2020;14:592607. doi: 10.3389/fncel.2020.592607
  8. Hesse R, Hurtado ML, Jackson RJ, et al. Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype. Acta Neuropathologica Commun. 2019;7:214. doi: 10.1186/s40478-019-0847-7
  9. Rajendran L, Paolicelli RC. Microglia-mediated synapse loss in Alzheimer’s disease. J Neurosci. 2018;38(12):2911–2919. doi: 10.1523/JNEUROSCI.1136-17.2017
  10. Martínez-Serra R, Alonso-Nanclares L, Cho K, Giese KP. Emerging insights into synapse dysregulation in Alzheimer’s disease. Brain Commun. 2022;4(2):fcac083. doi: 10.1093/braincomms/fcac083
  11. Griffiths J, Grant SGN. Synapse pathology in Alzheimer’s disease. Semin Cell Dev Biol. 2023;139:13–23. doi: 10.1016/j.semcdb.2022.05.028
  12. Yasuhara O, Kawamata T, Aimi Y, et al. Two types of dystrophic neurites in senile plaques of Alzheimer disease and elderly non-demented cases. Neurosci Lett. 1994;171(1-2):73–76. doi: 10.1016/0304-3940(94)90608-4
  13. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):32. doi: 10.1186/s13024-019-0333-5
  14. Sanchez-Varo R, Trujillo-Estrada L, Sanchez-Mejias E, et al. Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus. Acta Neuropathol. 2012;123(1):53–70. doi: 10.1007/s00401-011-0896-x
  15. Sadleir KR, Kandalepas PC, Buggia-Prévot V, et al. Presynaptic dystrophic neurites surrounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased Aβ generation in Alzheimer’s disease. Acta Neuropathol. 2016;132(2):235–256. doi: 10.1007/s00401-016-1558-9
  16. Kolos YeA, Grigoriyev IP, Korzhevskyi DE. A synaptic marker synaptophysin. Morphology. 2015;147(1):78–82. EDN: TIJLST doi: 10.17816/morph.398838
  17. Gudi V, Gai L, Herder V, et al. Synaptophysin is a reliable marker for axonal damage. J Neuropathol Exp Neurol. 2017;76(2):109–125. doi: 10.1093/jnen/nlw114
  18. Carson RE, Naganawa M, Toyonaga T, et al. Imaging of synaptic density in neurodegenerative disorders. J Nucl Med. 2022;63(Suppl. 1):60S–67S. doi: 10.2967/jnumed.121.263201
  19. Snow PM, Patel NH, Harrelson AL, Goodman CS. Neural-specific carbohydrate moiety shared by many surface glycoproteins in Drosophila and grasshopper embryos. J Neurosci. 1987;7(12):4137–4144. doi: 10.1523/JNEUROSCI.07-12-04137.1987
  20. Nosova OI, Guselnikova VV, Korzhevskii DE. Light microscopy approach for simultaneous identification of glial cells and amyloid plaques. Cell and Tissue Biology. 2022;16(2):140–149. EDN: EUVGGX doi: 10.1134/S1990519X22020080
  21. Guselnikova VV. Comparative analysis of histological methods used for identification of amyloid plaques in the human brain. Genes and cells. 2020;15(S3):158–159. EDN: MREAMV doi: 10.23868/gc123163
  22. Guselnikova VV, Antipova MV, Fedorova EA, et al. Distinctive features of histochemical and immunohistochemical techniques for amyloid plaque. Journal of Anatomy and Histopathology. 2019;8(2):91–99. EDN: YJHMVM doi: 10.18499/2225-7357-2019-8-2-91-99
  23. Pirici D, Margaritescu C. Corpora amylacea in aging brain and age-related brain disorders. J Aging Gerontol. 2014;2(1):33–57. doi: 10.12974/2309-6128.2014.02.01.6
  24. Navarro PP, Genoud C, Castaño-Díez D, et al. Cerebral Corpora amylacea are dense membranous labyrinths containing structurally preserved cell organelles. Sci Rep. 2018;8(1):18046. doi: 10.1038/s41598-018-36223-4
  25. Augé E, Bechmann I, Llor N, et al. Corpora amylacea in human hippocampal brain tissue are intracellular bodies that exhibit a homogeneous distribution of neo-epitopes. Sci Rep. 2019;9(1):2063. doi: 10.1038/s41598-018-38010-7
  26. Singhrao SK, Neal JW, Newman GR. Corpora amylacea could be an indicator of neurodegeneration. Neuropathol Appl Neurobiol. 1993;19(3):269–276. doi: 10.1111/j.1365-2990.1993.tb00437.x
  27. Takahashi K, Iwata K, Nakamura H. Intra-axonal corpora amylacea in the CNS. Acta Neuropathol. 1977;37(2):165–167. doi: 10.1007/BF00692062
  28. DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol. 1990;27(5):457–464. doi: 10.1002/ana.410270502

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2. Fig. 1. Synaptophysin-immunopositive structures in the human cerebral cortex with amyloid plaques. Immunohistochemical reaction for synaptophysin (brown) with Alcian blue counterstaining (blue). Fig. b is an enlarged fragment of Fig. a (yellow frame). The arrowheads indicate abnormal synaptophysin-containing structures associated with amyloid plaques. The distance line in Fig. c is 11.2 µm. The scale bar is 50 µm (a) and 20 µm (b–d)

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3. Fig. 2. Amyloid plaques and corpora amylacea in the human cerebral cortex: spatial relationship with synaptic structures. Immunohistochemical reaction for synaptophysin (brown) with Alcian blue counterstaining (blue). The arrows indicate corpora amylacea. The arrowheads indicate abnormal synaptophysin-containing structures associated with amyloid plaques. The scale bar is 50 µm (a), 20 µm (b) and 10 µm (a, yellow frame)

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