Abstract
Synapsin I is a synaptic vesicle-associated protein, participating in synapse formation, regulation of the synthesis of other synaptic vesicle proteins and promotion of neurotransmitter release. The aim of present study was to detect whether regional alteration of synapsin I occurred in the hippocampal formation of Alzheimer’s disease (AD) patients. Samples of hippocampus from ten female AD patients and ten non-demented female controls, matched for age and postmortem delay, were investigated immunocytochemically. Using immunofluorescence labeling and laser confocal imaging, we examined the distribution of synapsin I in the CA1 and CA3 subfields of the hippocampus and the dentate gyrus (DG) in AD patients and controls. The results showed that synapsin I was significantly decreased in the stratum radiatum of CA1 subfield and the molecular layer of DG in AD patients. No difference between the two groups in the intensity of synapsin I staining was observed in the stratum pyramidale of CA1, where a number of pretangles stained by Alz-50 were observed in AD patients. These results suggest that there is regional loss of synapsin I in the hippocampal formation of AD patients.
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Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42:631–639
Callahan LM, Coleman PD (1995) Neurons bearing neurofibrillary tangles are responsible for selected synaptic deficits in Alzheimer’s disease. Neurobiol Aging 16:311–314
Callahan LM, Chow N, Cheetham JE, Cox C, Coleman PD (1998) Analysis of message expression in single neurons of Alzheimer’s disease brain. Neurobiol Aging 19(Suppl):S99–105
Chin LS, Li L, Ferreira A, Kosik KS, Greengard P (1995) Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proc Natl Acad Sci USA 92:9230–9234
DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5:417–421
Ferrer I, MartE I, Tortosa A, Blasi J (1998) Dystrophic neurites of senile plaques are defective in proteins involved in exocytosis and neurotransmission. J Neuropathol Exp Neurol 57: 218–225
Gallagher M, Nicolle MM (1993) Animal models of normal aging: relationship between cognitive decline and markers in hippocampal circuitry. Behav Brain Res 57:155–162
Greengard P, Valtorta F, Czernik AJ, Benfenati F (1993) Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 259: 780-785
Heinonen O, Soininen H, Sorvari H, Kosunen O, Paljarvi L, Koivisto E, Riekkinen-Sr PJ (1995) Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer’s disease. Neuroscience 64:375–384
Hosaka M, Sudhof TC (1998) Synapsin III, a novel synapsin with an unusual regulation by Ca2+. J Biol Chem 273: 13371–13374
Hu XY, Zhang HY, Qin S, Xu H, Swaab DF, Zhou JN (2002) Increased p75NTR expression in hippocampal neurons containing hyperphosphorylated tau in Alzheimer patients. Exp Neurol 178:104–111
Huttner WB, Schiebler W, Greengard P, De-Camilli P (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J Cell Biol 96:1374–1388
Hyman BT, Van-Horsen GW, Damasio AR, Barnes CL (1984) Alzheimer,s disease: cell-specific pathology isolates the hippocampal formatiom. Science 225:1168–1170
Hyman BT, Van-Hosen GW, Kromer J, Damasio AR (1986) Perforant pathway changes and the memory impairment of Alzheimer’s disease. Ann Neurol 20:472–481
Kao HT, Porton B, Czernik AJ, Feng J, Yiu G, Häring M, Benfenati F, Greengard P (1998) A third member of the synapsin gene family. Proc Natl Acad Sci USA 95: 4667–4672
Kao HT, Porton B, Hilfiker S, Stefani G, Pieribone VA, DeSalle R, Greengard P (1999) Molecular evolution of the synapsin gene family. J Exp Zool 285: 360–377
Ko LW, Ko EC, Nacharaju P, Liu WK, Chang E, Kenessey A, Yen SH (1999) An immunochemical study on tau glycation in paired helical filaments. Brain Res 830:301–313
Li L, Chin L, Shupliakov O, Brodin L, Sihra TS, Hvalby O, Jensen V, Zheng D, McNamara JO, Greengard P, Andersen P (1995) Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci USA 92:9235–9239
Masliah E, Honer WG, Mallory M, Voight M, Kushner P, Hansen L, Terry R (1994) Topographical distribution of synaptic-associated proteins in the neuritic plaques of Alzheimer’s disease hippocampus. Acta Neuropathol 87:135–142
Mukaetova-Ladinska EB, Garcia-Siera F, Hurt J, Gertz HJ, Xuereb JH, Hills R, Brayne C, Huppert FA, Paykel ES, McGee M, Jakes R, Honer WG, Harrington CR, Wischik CM (2000) Staging of cytoskeletal and β-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer’s disease. Am J Pathol 157:623–636
Nicoll RA, Kauer JA, Malenka RC (1988) The current excitement in long-term potentiation. Neuron 1:97–103
Rosene DL, Van-Hoesen GW (1987) The hippocampal formation of the primate brain: a review of some comparative aspects of cytoarchitecture and connections. In: Jones EG, Peters A (eds) Cerebral Cortex. Plenum Press, New York, pp 345–456
Salehi A, Ravid R, Gonatas NK, Swaab DF (1995) Decreased activity of hippocampal neurons in Alzheimer’s disease is not related to the presence of neurofibrillary tangles. J Neuropathol Exp Neurol 54:704–709
Scheff SW, Sparks DL, Price DA (1996) Quantitative assessment of synaptic density in the outer molecular layer of the hippocampal dentate gyrus in Alzheimer’s disease. Dementia 7:226–232
Shimohama S, Kamiya S, Taniguchi T, Akagawa K, Kimura J (1997) Differential involvement of synaptic vesicle and presynaptic plasma membrane proteins in Alzheimer’s disease. Biochem Biophys Res Commun 236:239–242
Smith MZ, Nagy Z, Barnetson L, King EM, Esiri MM (2000) Coexisting pathologies in the brain: influence of vascular disease and Parkinson’s disease on Alzheimer’s pathology in the hippocampus. Acta Neuropathol 100:87–94
Sorra KE, Harris KM (1993) Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1. J Neuronsci 13:3736–3748
Sze CI, Troncoso JC, Kawas K, Mouton P, Price DL, Martin J (1997) Loss of presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J Neuropathol Exp Neurol 56:933–944
Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ (2000) Selective regional loss of exocytotic presynaptic vesicle proteins in Alzheimer’s disease brains. J Neurol Sci 175:81–90
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580
Van de Nes JA, Sluiter AA, Pool CW, Kamphorst W, Ravid R, Swaab DF (1994) The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in Alzheimer’s disease, also reacts with a large subpopulation of somatostatin neurons in the normal human hypothalamus and adjoining areas. Brain Res 655:97–109
Yang-Feng TL, DeGennaro LJ, Francke U (1986) Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. Proc Natl Acad Sci USA 83: 8679–8683
Acknowledgements
We are grateful to the Netherlands Brain Bank for the brain material (coordinator, Dr. R. Ravid), to Mr. Zhen Guo for the help of confocal photomicrographs. This project was financially supported by the Innovation Project of the Science Academy of China (KSCX2-SW-217), the National Key Project for Basic Science of China (G1999054007) and the International Cooperation Project of China (2001CB711101).
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Qin, S., Hu, XY., Xu, H. et al. Regional alteration of synapsin I in the hippocampal formation of Alzheimer’s disease patients. Acta Neuropathol 107, 209–215 (2004). https://doi.org/10.1007/s00401-003-0800-4
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DOI: https://doi.org/10.1007/s00401-003-0800-4