Ultrastructural evidence that insoluble microtubules are components of the neurofibrillary tangle

Abstract

The ultrastructure of Alzheimer's neurofibrillary tangles is heterogeneous and includes abnormal paired helical filaments (PHF) and various other insoluble structures. Insoluble non-PHF components isolated from neurofibrillary tangles were examined by electron microscopy. Comparison of these fractions with normal assembled neurofilaments and normal brain microtubules revealed scattered profiles which were morphologically (not chemically) identical to structures present in the microtubule, but not in the neurofilament preparations. These results support the notion that insoluble microtubules contribute to the make up of the neurofibrillary tangle. Based on these findings, preliminary experiments were conducted which suggest that non-enzymatic glycosylation may be a pathway leading to insolubility of the microtubules.