Decreased Neurotrophic Support is Associated with Cognitive Decline in Non-Demented Subjects

Article type: Research Article

Authors: Forlenza, Orestes Vicente^a | Miranda, Aline Silva^b | Guimar, Izabela | Talib, Leda Leme^a | Diniz, Breno Satler^{c; d} | Gattaz, Wagner Farid^a | Teixeira, Antonio Lucio^{b; *}

Affiliations: [a] Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil | [b] Neuroscience Branch, Interdisciplinary Laboratory of Medical Investigation, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil | [c] Department of Mental Health, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil | [d] National Institute of Science & Technology Molecular Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

Correspondence: [*] Correspondence to: Antonio L. Teixeira, Laboratório Interdisciplinar de Investigação Médica, sala 281, Faculdade de Medicina, UFMG, Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, MG, 30130-100, Brasil. Tel.: +55 31 3409 8073; altexr@gmail.com

Abstract: Background: There is evidence of decreased neurotrophic support in Alzheimer’s disease (AD), including its prodromal stages, but it is not clear whether this abnormality represents a marker of this process. Objective: To determine serum concentrations of a panel of neurotrophic factors (BDNF, NGF, and GDNF) in a cross-section of elderly patients with mild cognitive impairment (MCI) and AD compared to cognitively healthy controls, and to evaluate whether abnormal levels of these factors at baseline predict the transition from MCI to dementia. Methods: A total of 134 older adults were enrolled in this study. Twenty-six patients with mild to moderate AD, 62 with MCI, and 46 cognitively healthy older adults (controls) were subjected to a clinical evaluation including several cognitive tests. Peripheral blood was drawn and serum levels of BDNF, NGF, and GDNF were measured by enzyme-linked immunosorbent assay. APOE genotyping was performed by PCR assays. Results: Serum concentrations of BDNF, NGF, and GDNF were significantly reduced in cognitively impaired subjects (i.e., MCI and AD) as compared to controls, although only the former two remained statistically different after controlling for age, gender, and cognitive performance (p = 0.05 and p = 0.01, respectively). Lower BDNF and NGF levels were also observed in the sub-sample of MCI patients who progressed to dementia upon follow-up (p = 0.02 and p = 0.002, respectively). Conclusion: Abnormalities in neurotrophic systems are observed at early stages of AD and may represent a marker of cognitive deterioration.

Keywords: Alzheimer’s disease, BDNF, GDNF, mild cognitive impairment, NGF, physiopathology

DOI: 10.3233/JAD-150172

Journal: Journal of Alzheimer's Disease, vol. 46, no. 2, pp. 423-429, 2015