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Decreased Levels of Brain-Derived Neurotrophic Factor and Increased Levels of Nerve Growth Factor in Hippocampus and Cortical Areas

Christoph Hock, MD; Klaus Heese, PhD; Christine Hulette, MD, PhD; Carlyn Rosenberg, MS; Uwe Otten, MD

Arch Neurol. 2000;57:846-851.

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.

From the Department of Psychiatry Research, University of Zürich, Zürich, Switzerland (Dr Hock); Department of Physiology, University of Basel, Basel, Switzerland (Drs Heese and Otten); and the Kathleen Price Bryan Brain Bank, Duke University Medical Center, Durham, NC (Drs Hulette and Ms Rosenberg). Dr Heese is now with Brain Function Research Institute Inc, National Cardiovascular Center, Osaka, Japan.

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