Fleecy amyloid deposits in the internal layers of the human entorhinal cortex are comprised of N-terminal truncated fragments of aβ

Abstract

The deposition of amyloid in the brain is a hallmark of Alzheimer disease (AD). Amyloid deposits consist of accumulations of β-amyloid (Aβ), which is a 39-43 amino-acid peptide cleaved from the Aβ-protein precursor (APP). Another cleavage product of APP is the P3-peptide, which consists of the amino acids 17-42 of the Aβ-peptide. In order to study the deposition of N-terminal truncated forms of Aβ in the human entorhinal cortex, serial sections from 16 autopsy cases with AD-related pathology were immunostained with antibodies against Aβ1-40, Aβ1-42, Aβ17-23, and Aβ8-17, as well as with the Campbell-Switzer silver impregnation for amyloid. In the external entorhinal layers (pre-β and pre-γ), sharply delineated diffuse plaques were seen. They were labeled by silver impregnation and by all Aβ-antibodies used. By comparison, in the internal layers (pri-α, pri- β, and pri-γ) blurred, ill-defined clouds of amyloid existed, in addition to sharply delineated diffuse plaques. These clouds of amyloid were termed 'fleecy amyloid'. Immunohistochemically, fleecy amyloid was stained by Aβ17-23 and Aβ1-42 antibodies, but not with antibodies against Aβ8-17 and Aβ1-40. Using the Campbell-Switzer technique, the fleecy amyloid deposits were found to be fine argyrophilic amyloid fibrils. Thus, the internal entorhinal layers are susceptible to a distinct type of amyloid, namely fleecy amyloid. This fleecy amyloid obviously corresponds to N- terminal truncated fragments of Aβ1-42, probably representing the P3- peptide. These N-terminal truncated fragments of Aβ are capable of creating fine fibrillar 'amyloid'.