Figure 2.

Modulation of the brain-derived neurotrophic factor (BDNF) functional interactome across Alzheimer’s disease (AD) stages at the level of olfactory bulb (OB).

Adaptation of BDNF functional network in initial AD (Braak I–II) (left), intermediate AD (Braak III–IV) (right) and advanced AD (Braak V–VI) (down). Continuous lines represent direct interactions, while discontinuous lines correspond to indirect functional interactions. Up-regulated molecules in red, and down-regulated molecules in green. (See complete legend in Additional file 1 ^{(158.3KB, pdf)} ). Deregulated proteins are mainly involved in regulation of neurotransmitter release (synaptosomal associated protein-25; SNAP25), dendrite formation (unconventional myosin Va; MYO5A), synaptic vesicle docking (syntaxin-binding protein 1; STXBP1, AP3-complex subunit delta-1; AP3D1), endocytic trafficking (Nck-associated protein 1; NCKAP1) and axon guidance (Plexin-B2; PLXNB2). In the case of PD, the altered BDNF interactors were polypyrimidine tract-binding protein 1 (PTBP1; common to limbic and neocortical stages), and Laminin subunit beta-2 (LAMB2), agrin (AGRN), interferon-induced, double-stranded RNA-activated protein kinase (EIF2AK2) and Guanine deaminase (GDA) (specifically modulated in neocortical stage).