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


CONCLUSIONS
Abnormalities in neurotrophic systems are observed at early stages of AD and may represent a marker of cognitive deterioration.
Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Orestes Vicente
OV
Forlenza
Neuroscience Branch, Interdisciplinary Laboratory of Medical Investigation, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Aline Silva
AS
Miranda
Izabela
I
Guimar
Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Leda Leme
LL
Talib
Department of Mental Health, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.|National Institute of Science & Technology Molecular Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Breno Satler
BS
Diniz
Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Wagner Farid
WF
Gattaz
Neuroscience Branch, Interdisciplinary Laboratory of Medical Investigation, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Antonio Lucio
AL
Teixeira
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D016022:Case-Control Studies; D003071:Cognition; D060825:Cognitive Dysfunction / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020932:Nerve Growth Factor / Q000097:blood; D009483:Neuropsychological Tests
D001057:Apolipoproteins E; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; C502240:NGF protein, human; C579455:BDNF protein, human; D020932:Nerve Growth Factor
Alzheimer’s disease; BDNF; GDNF; NGF; mild cognitive impairment; physiopathology