Region-Specific Neurotrophin Imbalances in Alzheimer Disease: Decreased Levels of Brain-Derived Neurotrophic Factor and Increased Levels of Nerve Growth Factor in Hippocampus and Cortical Areas
Abstract
BACKGROUND: Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5) are members of the neurotrophin gene family that support the survival of specific neuronal populations, including those that are affected by neurodegeneration in Alzheimer disease (AD). OBJECTIVE: To determine whether neurotrophin protein levels are altered in the AD-affected brain compared with control brains. METHODS: We quantitated protein levels of NGF, BDNF, NT-3, and NT-4/5, and calculated neurotrophin/NT-3 ratios in AD-affected postmortem hippocampus, frontal and parietal cortex, and cerebellum, and compared them with age-matched control tissue (patients with AD/controls: hippocampus, 9/9 cases; frontal cortex, 19/9; parietal cortex, 8/5; and cerebellum, 5/7, respectively). We applied highly sensitive and specific enzyme-linked immunosorbent assays in rapid-autopsy-derived brain tissue (mean+/-SD postmortem interval, 2. 57+/-1.75 h, n=71) to minimize postmortem proteolytic activity. RESULTS: Levels of BDNF were significantly reduced in hippocampus and parietal cortex (P<.001, and P<.01) as well as BDNF/NT-3 ratios in frontal and parietal cortices (P<.05, and P<.01) in the group with AD compared with the control group. Levels of NGF and NGF/NT-3 ratio were significantly elevated in the group with AD compared with the control group in the hippocampus and frontal cortex (P<.001). Levels of NT-4/5 and the NT-4/NT-3 ratio were slightly reduced in hippocampus and cerebellum in the group with AD compared with the control group (P<.05). In contrast, the levels of NT-3 were unchanged in all brain regions investigated. CONCLUSION: Decreased levels of BDNF may constitute a lack of trophic support and, thus, may contribute to the degeneration of specific neuronal populations in the AD-affected brain, including the basal forebrain cholinergic system. Arch Neurol. 2000.
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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.
“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 [242]
BDNF is significantly downregulated in post-mortem AD brains.
“Since BDNF is significantly downregulated in post-mortem AD brains”
From 2-Deoxyglucose drives plasticity via an adaptive ER stress-ATF4 pathway and elicits stroke recovery and Alzheimer’s resilience (2023) · cites this paper as [38]
Amounts of BDNF protein are reduced in the entorhinal cortex and hippocampus in Alzheimer's disease.
“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 [9]
Concentrations of BDNF decline in the entorhinal cortex and hippocampus in Alzheimer's disease.
“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 [9]
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“Multiple studies have revealed a drop in BDNF levels in AD patients (156-159), while other reports indicate an increase in BNDF expression compared to control (160), which could be a compensatory repair mechanism during early stages of AD.”
Result
- Authors
- Hock, C., Heese, K., Hulette, C., Rosenberg, C., & Otten, U.
- Affiliations
- Duke Medical Center (US)
- University of Basel (CH)
- ORCID
- Heese, Klaus
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2000-06-01
- Volume
- 57
- Issue
- 6
- Pages
- 846
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2073644964
- Cited by
- 523
- References
- 30
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 23 · 2023: 27 · 2022: 24 · 2021: 29 · 2020: 28 · 2019: 22 · 2018: 23 · 2017: 29 · 2016: 27 · 2015: 26 · 2014: 22 · 2013: 30 · 2012: 11
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50 AG05128, P50AG005128)
- Topics
- Health Sciences › Medicine › Physiology › 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, neurotrophin-4/5, hippocampus, cerebral cortex, cerebellum, postmortem brain, neurodegeneration, basal forebrain cholinergic system
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Cerebral Cortex, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Male, Middle Aged, Nerve Growth Factors, Brain-Derived Neurotrophic Factor, Neurotrophin 3
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