Background: Alzheimer´s disease is characterized by extracellular beta-amyloid plaques, intraneuronal tau neurofibrillary tangles and excessive neurodegeneration. The mechanisms of neuron degeneration and the potential of these neurons to form new nerve fibers for compensation remain elusive. The present study aimed to evaluate the impact of beta-amyloid and tau on new formations of nerve fibers from mouse organotypic brain slices connected to collagen-based microcontact prints.Methods: Organotypic mouse brain slices of postnatal day 8-10 mice were connected to established collagen-based microcontact prints loaded with poly-ornithine to enhance nerve fiber outgrowth. Human beta-amyloid(42) or P301S mutated aggregated tau was co-loaded to the prints. Nerve fibers were immunohistochemically stained with neurofilament or Tau5 antibodies. To demonstrate retrograde transport functionality, neurotracer MiniRuby crystals were applied to the microcontact-printed lanes. Results: Immunohistochemical staining revealed newly formed nerve fibers extending along the prints derived from the brain slices. While collagen-only microcontact prints stimulated nerve fiber growth, those loaded with poly-ornithine significantly enhanced nerve fiber outgrowth. Beta-amyloid(42) significantly increased the neurofilament-positive nerve fibers, while tau had only a weak effect. However, co-loading tau with poly-ornithine resulted in a significant additive effect. MiniRuby crystals retrogradely transported along these newly formed nerve fibers reached the hippocampus. Discussion: Our data provide evidence that intact nerve fibers can form along collagen-based microcontact prints from mouse brain slices. The Alzheimer’s peptide beta-amyloid(42) stimulates this growth. This “brain-on-chip” model may offer a platform for screening bioactive factors or testing drug effects on nerve fiber growth.