3D printing of beta-amyloid protein deposits along capillary walls

Abstract

Abnormally high levels of neocortical beta-amyloid protein (A+) reflect Alzheimer’s disease (AD) pathology in persons with clinical evidence of dementia or mild cognitive impairment (MCI). The abnormal aggregation of beta-amyloid protein in the brain neuropil may lead to either diffuse plaques and/or concentrated neuritic plaques, with the latter form of deposits often present in the vicinity of the cerebral microvasculature. The A protein, with its crystalline molecular structure, infiltrates the vessel walls and compromises the blood-brain barrier (BBB). The physical basis for this was elegantly shown by Meyer and colleagues, in a 2008 publication showing two-dimensional (2D) confocal laser scanning microscopic imaging of vascular A protein deposits in APP23 transgenic mice. These investigators showed accumulations of “tuft-life structures”, also referred to as “pompons” with protruding spikes on – and embedded within – microvessels. These pompons of beta-amyloid protein “consist of fibrillar structures, [and] can encircle and constrict capillaries, and are often associated with distortion of capillaries”.We were struck by both the heuristic value of the imaging of Meyer and colleagues, in explaining the root cause of both the amyloid-related alterations in the vascular bed, and depicting minute protein deposits that are both geometrically complex, seemingly delicate and fragile, and yet tenacious in their embedding within small vessel walls. We re-created these images with standard 3D printing technology (extruded plastic) for both educational/teaching and artistic purposes.