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Gene- and Gender-Related Decrease in Serum BDNF Levels in Alzheimer's Disease.

Daniela Piancatelli1, Anna Aureli1, Pierluigi Sebastiani1

  • 1National Research Council (CNR)-Institute of Translational Pharmacology (IFT), 67100 L'Aquila, Italy.

International Journal of Molecular Sciences
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Reduced serum Brain-Derived Neurotrophic Factor (BDNF) is linked to Alzheimer's disease (AD), especially in women. Specific gene variations in BDNF and IL-1α may influence these BDNF levels in AD patients.

Keywords:
Alzheimer’s diseasebrain-derived neurotrophic factor (BDNF)cytokinesgenderoxidative stress

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Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Brain-Derived Neurotrophic Factor (BDNF) plays a crucial role in neuronal survival and function, with potential protective effects in Alzheimer's disease (AD).
  • Oxidative stress and inflammatory cytokines are implicated in AD pathogenesis, suggesting complex interactions with neurotrophic factors.
  • Genetic variations in BDNF and related genes may influence susceptibility and progression of neurodegenerative diseases like AD.

Purpose of the Study:

  • To investigate serum BDNF levels in patients with AD and mild cognitive impairment (MCI).
  • To examine the association between serum BDNF levels and gene polymorphisms in BDNF, oxidative stress-related genes, and interleukin-1 family genes.
  • To explore potential gender-specific differences in these associations.

Main Methods:

  • Serum BDNF levels were measured in AD, MCI patients, and controls.
  • Genotyping was performed for BDNF (Val66Met, C270T), oxidative stress genes (FOXO3A, SIRT3, GLO1, SOD2), and IL-1 family genes (IL-1α, IL-1β, IL-38).
  • APOE status and Mini-Mental State Examination (MMSE) scores were assessed. Statistical analyses were conducted, including subgroup analyses by gender.

Main Results:

  • Serum BDNF levels were significantly lower in AD patients compared to controls (p = 0.029), particularly in females (p = 0.005).
  • Individuals with the BDNF Val/Val genotype showed significantly lower serum BDNF than controls (p = 0.010).
  • Lower BDNF levels in AD were associated with the IL-1α T mutant allele (rs1800587) (p = 0.040), with stronger associations observed in females.

Conclusions:

  • Reduced serum BDNF is a characteristic of AD, with a more pronounced effect observed in female patients.
  • Polymorphisms in the BDNF and IL-1α genes are associated with altered serum BDNF levels in AD, especially in women.
  • These findings highlight potential gender-related genetic factors influencing AD susceptibility and BDNF regulation.