Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer’s diseased brain
Abstract
The number and topographic distribution of immunocytochemically stained parvalbumin interneurons was determined in the hippocampal formation of control and Alzheimer's diseased brain. In control hippocampus, parvalbumin interneurons were aspiny and pleomorphic, with extensive dendritic arbors. In dentate gyrus, parvalbumin cells, as well as a dense plexus of fibers and puncta, were associated with the granule cell layer. A few cells also occupied the molecular layer. In strata oriens and pyramidale of CA1-CA3 subfields, parvalbumin neurons gave rise to dendrites that extended into adjacent strata. Densely stained puncta and beaded fibers occupied stratum pyramidale, with less dense staining in adjacent strata oriens and radiatum. Virtually no parvalbumin profiles were observed in stratum lacunosum-moleculare or the alveus. Numerous polymorphic parvalbumin neurons and a dense plexus of fibers and puncta characterized the deep layer of the subiculum and the lamina principalis externa of the presubiculum. In Alzheimer's diseased hippocampus, there was an approximate 60% decrease in the number of parvalbumin interneurons in the dentate gyrus/CA4 subfield (P<0.01) and subfields CA1-CA2 (P<0.01). In contrast, parvalbumin neurons did not statistically decline in subfields CA3, subiculum or presubiculum in Alzheimer's diseased brains relative to controls. Concurrent staining with Thioflavin-S histochemistry did not reveal degenerative changes within parvalbumin-stained profiles. These findings reveal that parvalbumin interneurons within specific hippocampal subfields are selectively vulnerable in Alzheimer's disease. This vulnerability may be related to their differential connectivity, e.g., those regions connectionally related to the cerebral cortex (dentate gyrus and CA1) are more vulnerable than those regions connectionally related to subcortical loci (subiculum and presubiculum).
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In the hippocampus of AD patients, a ~60% decrease of PV-positive interneurons has been detected in the dentate gyrus and CA1-CA2 subfields.
“In the hippocampus of AD patients, a ~60% decrease of PV-positive interneurons has been detected in the dentate gyrus and CA1–CA2 subfields [118]”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [118]
Cites
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499 · see citing works
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984) · Science · doi:10.1126/science.6474172 · Cited by 2,268 · see citing works
Calbindin D-28k and parvalbumin in the rat nervous system
Celio, M. R. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90091-h · Cited by 2,086 · see citing works
de Nó, R. L. (1934) · Cited by 1,974 · see citing works
Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.
Griffin, W. S., Stanley, L. C., Ling, C., White, L., MacLeod, V, Perrot, L. J., White, C. L., & Araoz, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7611 · Cited by 1,777 · see citing works
Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., & Powell, T. P. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4531 · Cited by 987 · see citing works
Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology
Watson, R. E., Wiegand, S. J., Clough, R. W., & Hoffman, G. E. (1986) · Peptides · doi:10.1016/0196-9781(86)90076-8 · Cited by 933 · see citing works
Parvalbumin in Most γ-Aminobutyric Acid-Containing Neurons of the Rat Cerebral Cortex
Celio, M. R. (1986) · Science · doi:10.1126/science.3945815 · Cited by 740 · see citing works
Hippocampal Efferents Reach Widespread Areas of Cerebral Cortex and Amygdala in the Rhesus Monkey
Rosene, D. L., & Hoesen, G. W. V. (1977) · Science · doi:10.1126/science.410102 · Cited by 678 · see citing works
Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists.
Mirra, S. S., Hart, M. N., & Terry, R. D. (1993) · PubMed · Cited by 412 · see citing works
Topographical organization of the entorhinal projection to the dentate gyrus of the monkey
Witter, M., Hoesen, G. W. V., & Amaral, D. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-01-00216.1989 · Cited by 380 · see citing works
Sloviter, R. S., Sollas, A. L., Barbaro, N. M., & Laxer, K. D. (1991) · Journal of Comparative Neurology · doi:10.1002/cne.903080306 · Cited by 349 · see citing works
Visualization of chandelier cell axons by parvalbumin immunoreactivity in monkey cerebral cortex.
DeFelipe, J., Hendry, S. H. C., & Jones, E. G. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.6.2093 · Cited by 338 · see citing works
Protection of Dentate Hilar Cells from Prolonged Stimulation by Intracellular Calcium Chelation
Scharfman, H. E., & Schwartzkroin, P. A. (1989) · Science · doi:10.1126/science.2508225 · Cited by 296 · see citing works
Chan‐Palay, V. (1987) · Journal of Comparative Neurology · doi:10.1002/cne.902600205 · Cited by 254 · see citing works
Katsumaru, H., Kosaka, T., Heizmann, C. W., & Hama, K. (1988) · Experimental Brain Research · doi:10.1007/bf00250256 · Cited by 249 · see citing works
Nitsch, C., Scotti, A. L., Sommacal, A., & Kalt, G. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90631-9 · Cited by 211 · see citing works
HOF, P. R., COX, K., Young, W. G., Celio, M. R., Rogers, J., & Morrison, J. H. (1991) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199107000-00006 · Cited by 188 · see citing works
Stichel, C. C., Singer, W., Heizmann, C. W., & Norman, A. W. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902620409 · Cited by 172 · see citing works
Seress, L., Gulyás, A. I., Ferrer, I., Tuñón, T., Soriano, E., & Freund, T. F. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903370204 · Cited by 130 · see citing works
Diagnosis of Alzheimer's Disease
Reisberg, ., & Burns, A. S. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297004651 · Cited by 126 · see citing works
Loss of parvalbumin-immunoreactive neurones from cortex in Alzheimer-type dementia
Arai, H., Emson, P. C., Mountjoy, C. Q., Carassco, L. H., & Heizmann, C. W. (1987) · Brain Research · doi:10.1016/0006-8993(87)90974-7 · Cited by 118 · see citing works
Satoh, J., Tabira, T., Sano, M., Nakayama, H., & Tateishi, J. (1991) · Acta Neuropathologica · doi:10.1007/bf00293459 · Cited by 98 · see citing works
Chan‐Palay, V., Köhler, C., Haesler, U., Lang, W., & Yasargil, G. M. (1986) · The Journal of Comparative Neurology · doi:10.1002/cne.902480306 · Cited by 97 · see citing works
Parvalbumin-immunoreactive structures in the hippocampus of the human adult
Braak, E., Strotkamp, B., & Braak, H. (1991) · Cell and Tissue Research · doi:10.1007/bf00305720 · Cited by 94 · see citing works
Fonseca, M., Soriano, E., Ferrer, I., Martı́nez, A., & Tun˜on, T. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90324-9 · Cited by 88 · see citing works
Pitkänen, A., & Amaral, D. G. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903310104 · Cited by 85 · see citing works
Waldvogel, H. J., Faull, R. L. M., Williams, M. N., & Dragunow, M. (1991) · Brain Research · doi:10.1016/0006-8993(91)91497-o · Cited by 76 · see citing works
Dawbarn, D., Rossor, M. N., Mountjoy, C. Q., Roth, M., & Emson, P. C. (1986) · Neuroscience Letters · doi:10.1016/0304-3940(86)90455-6 · Cited by 75 · see citing works
Ferrer, I., Soriano, E., Tuñón, T., Fonseca, M., & Guionnet, N. (1991) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(91)90250-b · Cited by 72 · see citing works
Gaspar, P., Duyckaerts, C. J., Febvret, A., Benoit, R., Beck, B., & Berger, B. (1989) · Brain Research · doi:10.1016/0006-8993(89)90424-1 · Cited by 65 · see citing works
Transmitter systems in the primate dentate gyrus.
Amaral, D. G., & Campbell, M. J. (1986) · PubMed · Cited by 65 · see citing works
Amygdaloid Pathology in Alzheimer's Disease: Qualitative and Quantitative Analysis
Brady, D. R., & Mufson, E. J. (1990) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000107115 · Cited by 63 · see citing works
Self-citationImmunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia
Leifer, D., & Kowall, N. W. (1993) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(93)90137-n · Cited by 57 · see citing works
Berchtold, M. W., Celio, M. R., & Heizmann, C. W. (1985) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1985.tb05498.x · Cited by 57 · see citing works
Nitsch, R., Léránth, C., & Frotscher, M. (1990) · Brain Research · doi:10.1016/0006-8993(90)91676-8 · Cited by 43 · see citing works
Distribution of immunoreactive cholecystokinin in the human hippocampus
Lotstra, F., & Vanderhaeghen, J. (1987) · Peptides · doi:10.1016/0196-9781(87)90080-5 · Cited by 38 · see citing works
Alz‐50 immunoreactive neuropil differentiates hippocampal complex subfields in Alzheimer's disease
Brady, D. R., & Mufson, E. J. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903050311 · Cited by 38 · see citing works
Self-citationIwamoto, N., & Emson, P. C. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90764-k · Cited by 32 · see citing works
Nitsch, R., & Léránth, C. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903090403 · Cited by 29 · see citing works
Inaguma, Y., Shinohara, H., Inagaki, T., & Kato, K. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90009-a · Cited by 27 · see citing works
Ferrer, I., Zujar, M. J., Rivera, R., Soria, M. T., Vidal, A., & Casas, R. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90254-i · Cited by 22 · see citing works
Distribution of parvalbumin immunoreactivity in the human brain
Ohshima, T., Endo, T., & Onaya, T. (1991) · Journal of Neurology · doi:10.1007/bf00315329 · Cited by 21 · see citing works
Parvalbumin-Immunoreactive Neurons in the Normal Human Hippocampus
Höchli, M., Zetzsche, D. A., & Chan‐Palay, V. (1991) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000107212 · Cited by 6 · see citing works
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Rappert, A., Bechmann, I., Pivneva, T., Mahlo, J., Biber, K., Nolte, C., Kovac, A. D., Gerard, C., Boddeke, H. W. G. M., Nitsch, R., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2451-04.2004 · Cited by 259 · see citing works
Brückner, G., Hausen, D., Härtig, W., Drlicek, M., Arendt, T., & Brauer, K. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00071-8 · Cited by 196 · see citing works
Piskorowski, R. A., Nasrallah, K., Diamantopoulou, A., Mukai, J., Hassan, S. I., Siegelbaum, S. A., Gogos, J. A., & Chevaleyre, V. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.036 · Cited by 180 · see citing works
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Takahashi, H., Brasnjevic, I., Rutten, B. P. F., Van Der Kolk, N., Perl, D. P., Bouras, C., Steinbusch, H. W. M., Schmitz, C., Hof, P. R., & Dickstein, D. L. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0242-4 · Cited by 124 · see citing works
Gómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112 · see citing works
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Saiz-Sanchez, D., De la Rosa-Prieto, C., Ubeda-Banon, I., & Martinez-Marcos, A. (2015) · Brain Structure and Function · doi:10.1007/s00429-014-0771-3 · Cited by 79 · see citing works
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“In the hippocampus of AD patients, a ~60% decrease of PV-positive interneurons has been detected in the dentate gyrus and CA1–CA2 subfields [118] and related findings were reported in the perirhinal cortex [119].”
BackgroundMilenkovic, I., Vasiljevic, M., Maurer, D., Höger, H., Klausberger, T., & Sieghart, W. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.09.019 · Cited by 62 · see citing works
Zallo, F., Gardenal, E., Verkhratsky, A., & Rodríguez, J. J. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.05.027 · Cited by 57 · see citing works
Giesers, N. K., & Wirths, O. (2020) · ASN Neuro · doi:10.1177/1759091420925356 · Cited by 47 · see citing works
Belbin, O., Xiao, M.-F., Xu, D., Carmona-Iragui, M., Pegueroles, J., Benejam, B., Videla, L., Fernández, S., Barroeta, I., Nuñez-Llaves, R., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00398-0 · Cited by 39 · see citing works
Popović, M., Caballero-Bleda, M., Kadish, I., & Van Groen, T. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.05.023 · Cited by 38 · see citing works
Verdaguer, E., Brox, S., Petrov, D., Olloquequi, J., Romero, R., de Lemos, M. L., Camins, A., & Auladell, C. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.06.013 · Cited by 38 · see citing works
Lemmens, M. A. M., Sierksma, A. S. R., Rutten, B. P. F., Dennissen, F., Steinbusch, H. W. M., Lucassen, P. J., & Schmitz, C. (2011) · Brain Structure and Function · doi:10.1007/s00429-011-0305-1 · Cited by 37 · see citing works
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Franklin, S. L., Love, S., Greene, J. R. T., & Betmouni, S. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181654386 · Cited by 33 · see citing works
- Authors
- Brady, D. R., & Mufson, E. J.
- Affiliations
- National Institutes of Health (US)
- Rush University Medical Center (US)
- Corresponding author
- Brady, D.R
- ORCID
- Mufson, E.J
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 80
- Issue
- 4
- Pages
- 1113-1125
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2082796074
- Cited by
- 125
- References
- 44
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 16 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01ns026146-04, 5r01ag011482-03)
- National Institute on Aging (AG 11482, AG10688)
- National Institute of Neurological Disorders and Stroke (NS 26146)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- parvalbumin, interneurons, Alzheimer's disease, hippocampal formation, dentate gyrus, subiculum, presubiculum, neuronal vulnerability, topographic distribution, dendritic branching, thioflavin S staining, neuronal connectivity
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Fibers, Neurons, Parvalbumins, Reference Values, Pyramidal Cells, Dentate Gyrus
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