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Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimerʼs disease
Abstract
Using two-site enzyme immunoassays (EIAs), we measured the levels of neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) simultaneously in three brain regions (motor cortex, dentate gyrus and entorhinal cortex) of patients with Alzheimer's disease (AD) and control individuals. Significant differences between the neurotrophin levels of these two groups were found in the different brain regions depending on the neurotrophin. The NGF level in the dentate gyrus of AD patients was higher, whereas the BDNF level in the entorhinal cortex and the NT-3 level in the motor cortex were lower than the corresponding control levels. These results indicate that protein levels of individual neurotrophins in different brain regions are affected differently by AD, and such differential changes may contribute to the complex pathology of AD.
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“A reduced level of BDNF has been found in patients affected by neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s disease as well as in mild cognitive impairment, the latter being a prodromal stage of AD, characterized by a slight decline of cognitive abilities including memory, thinking and judging skills [242,243,244,245].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [244]
In the citing paper
“Furthermore, amounts of BDNF protein are reduced in the entorhinal cortex and hippocampus in Alzheimer’s disease7–9.”
From Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease (2009) · cites this paper as [7]
In the citing paper
“Notably, the concentrations of BDNF decline in the entorhinal cortex and hippocampus in Alzheimer’s disease7–9”
From Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease (2009) · cites this paper as [7]
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BDNF and Activity-Dependent Synaptic Modulation: Figure 1.
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BackgroundBrain-derived neurotrophic factor in neurodegenerative diseases
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Self-citationNeurotrophic factors in Alzheimer’s disease: role of axonal transport
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“2004) and in hippocampus (Hock et al. 2000a; Narisawa-Saito et al. 1996; Scott et al. 1995), while a loss is observed in the basal forebrain (Mufson et al.”
BackgroundInfluentialBrain-derived neurotrophic factor in Huntington disease
Ferrer, I., Goutan, E., Marı́n, C., Rey, M. J., & Ribalta, T. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02237-x · Cited by 333
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Estrogen–BDNF interactions: Implications for neurodegenerative diseases
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“Alzheimer’s ↓protein expression [22,34,46,80, 89] ↓risk for AD [92,125,146]”
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“In patients with AD, low BDNF levels have also been reported in the dentate gyrus and in neurons that have neurofibrillary tangles, a hallmark of AD [63,64].”
BackgroundThe exercise-induced expression of BDNF within the hippocampus varies across life-span
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“We analyzed the secretion of the important memoryrelated neurotrophin brain-derived neurotrophic factor (BDNF), a protein shown to be decreased in the brain of AD-patients [59, 60], and of the inflammatory (M1) cytokines IL-6 and tumor necrosis factor (TNF)- , shown to be increased in AD [3, 61].”
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“Several of the neurotrophins released by stem cells, including brain-derived neurotrophic factor, are decreased in the AD brain (Connor et al., 1997; Narisawa-Saito et al., 1996; Cattaneo et al., 2008).”
Stranahan, A. M., & Mattson, M. P. (2010) · Neural Plasticity · doi:10.1155/2010/108190 · Cited by 198
“Moreover, levels of BDNF are reduced in the entorhinal cortex in AD [41], and viral vectormediated expression BDNF ameliorated memory and synaptic LTP deficits in a rat dementia model in which synapsespecific lesions were induced by botulinum toxin [42].”
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Early BDNF Treatment Ameliorates Cell Loss in the Entorhinal Cortex of APP Transgenic Mice
Nagahara, A. H., Mateling, M., Kovács, I., Wang, L., Eggert, S., Rockenstein, E. M., Koo, E. H., Masliah, E., & Tuszynski, M. H. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5195-12.2013 · Cited by 176
“Moreover, BDNF levels decline in AD (Narisawa-Saito et al., 1996; Connor et al., 1997; Hock et al., 2000).”
The Neurotrophins and Their Role in Alzheimers Disease
Allen, S. J., Watson, J. J., & Dawbarn, D. (2011) · Current Neuropharmacology · doi:10.2174/157015911798376190 · Cited by 184
“BDNF mRNA levels in Alzheimer’s disease hippocampus [142] and parietal cortex [143] and decreased protein levels of BDNF in entorhinal cortex, hippocampus, temporal, frontal and parietal cortex [144-147].”
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“…entorhinal cortex, hippocampal formation, temporal cortex, parietal cortex, and the frontal cortex by multiple groups using either ELISA, immunohistochemistry, or western blot (Narisawa-Saito et al. 1996; Connor et al. 1997; Ferrer et al. 1999; Hock et al. 2000; Lee et al. 2005; Peng et al. 2005).”
MethodBrain‐derived neurotrophic factor and neurotrophin‐3 levels in Alzheimer's disease brains
Durany, N., Michel, T. M., Kurt, J., Cruz-Sánchez, F., Cervós‐Navarro, J., & Riederer, P. F. (2000) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(00)00046-0 · Cited by 155
“Further studies investigating other neurotrophic factors have demonstrated that NGF is significantly increased in frontal cortex, occipital cortex and dentate gyrus of AD compared to control subjects [11,28], but not in parietal Table 4 NT-3 concentrations in the various brain regions in Alzheimer’s patients and contr…”
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Mitochondria, Estrogen and Female Brain Aging
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“…to decrease in brain regions involved in age-related neurodegenerative diseases: e.g., in Alzheimer’s disease (AD) in the frontal cortex (Ferrer et al., 1999), the hippocampus (Phillips et al., 1991), the parietal cortex (Hock et al., 2000) and the entorhinal cortex (Narisawa-Saito et al., 1996).”
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“In fact, depending on the regions studied, the levels of different neurotrophins in AD patients may vary significantly [29,34].”
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Self-citationBrain-derived neurotrophic factor as a drug target for CNS disorders
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“Furthermore, decreased BDNF protein and pro-BDNF protein concentrations [20] have been found in the parietal cortex; reduced BDNF-immunoreactivity has been found in the entorhinal cortex [21,22], the dentate gyrus, the hilus and temporal cortex [23,24].”
BackgroundHsiao, Y.-H., Hung, H.-C., Chen, S.-H., & Gean, P.-W. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0747-14.2014 · Cited by 130
“Social interaction with a helper increases BDNF protein and mRNA levels in the hippocampus of the APP/PS1 mice Selective reduction of Bdnf mRNA and protein levels in the hippocampus has been reported in AD patients (Phillips et al., 1991; Narisawa-Saito et al., 1996; Ferrer et al., 1999; Zuccato and Cattaneo, 2009).”
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ProNGF and Neurodegeneration in Alzheimer’s Disease
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Neurotrophic factors and Alzheimer’s disease: are we focusing on the wrong molecule?
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“Secondly, although several groups have shown that BDNF protein also is reduced in AD target tissues, the results obtained using ELISA, immunohistochemistry, and Western blotting are not always in agreement (Connor et al., 1997; Ferrer et al., 1999; Narisawa-Saito et al., 1996).”
BackgroundDecreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms
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“Likewise, elevated NGF levels in the hippocampus and the frontal, temporoparietal and occipital cortex of post-mortem AD brains were reported when compared to normal controls (Crutcher et al., 1993; Narisawa-Saito et al., 1996; Hellweg et al., 1998a; Hock et al., 2000a).”
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“The amount and effectiveness of the neurotrophic factors in the brain were found to be decreased during the process of aging, and the decrease was robust in the pathological condition of Parkinson’s and Alzheimer’s diseases [9, 10].”
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“Moreover, relative levels of BDNF mRNA and proteins are decreased in frontal (Ferrer et al., 1999), temporal (Connor et al., 1997), parietal (Garzon et al., 2002; Michalski and Fahnestock, 2003) and entorhinal cortex (Narisawa-saito et al., 1996) in severe AD.”
BackgroundSystemic and Acquired Immune Responses in Alzheimer's Disease
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Brain-derived neurotrophic factor gene polymorphisms and Alzheimer?s disease
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“, 2000), and lower levels of BDNF protein have been reported in the entorhinal cortex (Narisawa-Saito et al., 1996) and in the hippocampus and parietal cortex (Hock et al.”
Nerve Growth Factor Gene Therapy in Alzheimer Disease
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Gene therapy in Alzheimer’s disease – potential for disease modification
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“Decreased NGF immunoreactivity in the basal forebrain of AD patients and increased NGF protein in the cerebral cortex and hippocampus have been demonstrated using bioassay and ELISA (796-800).”
MethodTherapeutic Potential of Neurotrophic Factors in Neurodegenerative Diseases
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Nerve Growth Factor Pathobiology During the Progression of Alzheimer’s Disease
Mufson, E. J., Counts, S., Ginsberg, S. D., Mahady, L. J., Perez, S. E., Massa, S. M., Longo, F. M., & Ikonomović, M. D. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00533 · Cited by 94
“, 1998) or increased (Crutcher et al., 1993; Scott et al., 1995; Fahnestock et al., 1996; Narisawa-Saito et al., 1996; Hellweg et al., 1998; Hock et al., 2000) NGF levels using tissue from severe AD subjects.”
BackgroundNerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease
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“…human and rodent brain, are doubled in frontal and occipital cortex and in hippocampus in late-stage AD (Crutcher et al., 1993; Scott et al., 1995; Narisawa-Saito et al., 1996; Hellweg et al., 1998; Hock et al., 2000; Fahnestock et al., 2001; Peng et al., 2004) and appear to be 40%–50% increased…”
BackgroundPhenotypic down-regulation of glutamate receptor subunit GluR1 in Alzheimer's disease
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Self-citationMolecular Basis of Neurotrophin−Receptor Interactions
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DNA methylation alterations in Alzheimer’s disease
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Challenges of BDNF-based therapies: From common to rare diseases
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“However, NGF levels vary in different brain regions, being the highest in the dentate gyrus of AD patients compared to healthy subjects [77].”
BackgroundDu, Y., Wu, H., Qin, X., Cao, C. Q., Liu, Y., Cao, Z.-Z., & Cheng, Y. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1100-8 · Cited by 80
Pramanik, S., Sulistio, Y. A., & Heese, K. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0214-7 · Cited by 77
Mariga, A., Mitre, M., & Chao, M. V. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.03.009 · Cited by 80
Increased IL-1β in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase
Maher, F. O., Martin, D. S. D., & Lynch, M. A. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.08.007 · Cited by 73
Roles of p75NTR in the pathogenesis of Alzheimer's disease: A novel therapeutic target
Zeng, F., Lu, J., Zhou, X., & Wang, Y. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.040 · Cited by 69
García‐Sierra, F., Wischik, C. M., Harrington, C. R., Luna‐Muñoz, J., & Mena, R. (2001) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(01)00096-5 · Cited by 72
Hromádková, L., Bezděková, D., Pala, J., Schedin‐Weiss, S., Tjernberg, L. O., Höschl, C., & Ovsepian, S. V. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118737 · Cited by 75
Brain-derived neurotrophic factor: a bridge between major depression and Alzheimer’s disease?
Tsai, S. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00141-5 · Cited by 67
Neurotrophins - From Pathophysiology to Treatment in Alzheimers Disease
Hellweg, R., Schulte‐Herbrüggen, O., & Jockers-Scherübl, M. C. (2008) · Current Alzheimer Research · doi:10.2174/156720508783884620 · Cited by 66
“Similar to BDNF, immunoreactive levels of NT-3 were found decreased in the cortex of AD patients compared to the corresponding brain regions in non-demented controls [71, 73] or they were found unchanged [72].”
ResultSreenivasmurthy, S. G., Liu, J., Song, J., Yang, C., Malampati, S., Wang, Z., Huang, Y., & Li, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020272 · Cited by 67
Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease
Bharani, K., Ledreux, A., Gilmore, A., Carroll, S. L., & Granholm, A. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.11.010 · Cited by 66
Neurotrophic activities and therapeutic experience with a brain derived peptide preparation
Windisch, M., Gschanes, A., & Hutter‐Paier, B. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6467-9_25 · Cited by 66
Fang, H., Chartier, J., Sodja, C., Desbois, A., Ribecco‐Lutkiewicz, M., Walker, P. R., & Sikorska, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211539200 · Cited by 61
Corbett, G. T., Roy, A., & Pahan, K. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.426536 · Cited by 63
Hellweg, R., von Richthofen, S., Anders, D., Baethge, C., Röpke, S., Hartung, H.-D., & Gericke, C. A. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050100 · Cited by 59
“patients by several research groups (Crutcher et al., 1993; Scott et al., 1995; Narisawa-Saito et al., 1996; Fahnestock et al., 1996; Gericke, 1996; Hellweg et al., 1998).”
BackgroundResultInfluentialPreservation of Brain Nerve Growth Factor in Mild Cognitive Impairment and Alzheimer Disease
Mufson, E. J., Ikonomović, M. D., Styren, S. D., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.8.1143 · Cited by 59
Essential Roles of Heparin‐Binding Epidermal Growth Factor‐Like Growth Factor in the Brain
Oyagi, A., & Hara, H. (2012) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2012.00371.x · Cited by 58
Combarros, O., Warden, D. R., Hammond, N., Cortina‐Borja, M., Belbin, O., Lehmann, M. G., Wilcock, G. K., Brown, K. S., Kehoe, P. G., Barber, R., et al. (2010) · BMC Medical Genetics · doi:10.1186/1471-2350-11-162 · Cited by 57
“BDNF levels have been found to be decreased in the postmortem hippocampus and neocortex [74-76] in AD.”
BackgroundLilja, A. M., Luo, Y., Yu, Q., Röjdner, J., Li, Y., Marini, A. M., Marutle, A., Nordberg, A. K., & Greig, N. H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054887 · Cited by 57
“BDNF plays a pivotal role in neuronal development and for synaptic plasticity [40,41], and levels of BDNF are decreased in the entorhinal cortex and the hippocampus in the AD brain [12,42,43].”
Background
Metadata
- Authors
- Narisawa-Saito, M., Wakabayashi, K., Tsuji, S., Takahashi, H., & Nawa, H.
- Affiliations
- Brain Research Institute, Niigata University (JP)
- Venue
- NeuroReport
- Published
- 1996-11
- Volume
- 7
- Issue
- 18
- Pages
- 2925-2928
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W2055746351
- Cited by
- 226
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 12 · 2015: 6 · 2014: 9 · 2013: 15 · 2012: 10
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, neurotrophins, nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, regional brain differences, dentate gyrus, entorhinal cortex, motor cortex
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain Chemistry, Humans, Immunoenzyme Techniques, Middle Aged, Nerve Growth Factors, Postmortem Changes, Rats, Sprague-Dawley, Entorhinal Cortex, Dentate Gyrus, Brain-Derived Neurotrophic Factor, Neurotrophin 3, Rats
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