Distinct Patterns Link the BDNF Val66Met Polymorphism to Alzheimer's Disease Pathology

The brain-derived neurotropic growth factor (BDNF) gene has been linked to dementia, inflammation, and Apolipoprotein E (APOE) epsilon 4 status. We used cerebrospinal fluid (CSF) amyloid-beta (A beta)(42) and phosphorylated tau (p-tau) to investigate associations with BDNF polymorphisms and modifications by APOE epsilon 4 or inflammation in a memory clinic population (n = 114; subjective cognitive decline, mild cognitive impairment, Alzheimer's disease). We found distinct pathways to Alzheimer's disease pathology: Val-Met displayed lower CSF-A beta(42) in APOE epsilon 4+ carriers, independent of p-tau, while Val-Val displayed greater p-tau at higher IL-6 and sub-threshold A beta(42). This may contribute to resolving some inconsistencies in the BDNF literature and provide possible inroads to specific A beta and tau interventions depending on BDNF polymorphism.

Automated summary

This study investigates the associations between BDNF gene polymorphisms and APOE ε4 status or inflammation in a memory clinic population, and finds distinct pathways to Alzheimer's disease pathology. These findings help resolve inconsistencies in the BDNF literature and provide possible specific interventions for Aβ and tau based on BDNF polymorphisms.