Cytoskeletal pathologies of Alzheimer disease

Abstract

The histopathological hallmarks of Alzheimer disease are the extracellular amyloid plaques, composed principally of the amyloid beta peptide, and the intracellular neurofibrillary tangles, composed of paired helical filaments of the microtubule-associated protein, tau. Other histopathological structures involving actin and the actin-binding protein, cofilin, have more recently been recognized. Here we review new findings about these cytoskeletal pathologies, and, emphasize how plaques, tangles, the actin-containing inclusions and their respective building blocks may contribute to Alzheimer pathogenesis and the primary behavioral symptoms of the disease. Cell Motil. Cytoskeleton, 2009. (c) 2009 Wiley-Liss, Inc.

Figure 1. Pathological features of human AD brain as seen by electron microscopy

(A). Extracellular amyloid plaque. (B) Tau-containing 20 nm wide paired helical filaments; the twisted ribbon-like structure is better seen in the magnified inset. (C) A likely cofilin-actin rod with a morphology identical to those induced in rat brain organotypic slices (Davis et al., 2009). Inset at higher magnification shows filaments are thinner (8-9 nm) than paired helical filaments. Images were kindly provided by Judy Boyle (A and B) and George Perry and Sandra Siedlak (C).