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Author Spotlight: Exploring Sex-Specific Glial Signatures and Therapeutic Leads for Alzheimer's Disease
Published on: May 20, 2024
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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
|December 11, 2022
Summary
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.
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.
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