Fleecy Amyloid Deposits in the Internal Layers of the Human Entorhinal Cortex are Comprised of N-terminal Truncated Fragments of Aβ

The deposition of amyloid in the brain is a hallmark of Alzheimer disease (AD). Amyloid deposits consist of accumulations of β-amyloid (AP), which is a 39-43 amino-acid peptide cleaved from the A(3-protein precursor (APP). Another cleavage product of APP is the P3-peptide, which consists of the amino acids 17-42 of the Ap-peptide. In order to study the deposition of N-terminal truncated forms of Ap in the human entorhinal cortex, serial sections from 16 autopsy cases with ADrelated 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 (preβ- 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 (priα, 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 Aβ8-10 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 Aβ1-12, probably representing the P3-peptide. These N-terminal truncated fragments of Aβ are capable of creating fine fibrillar “amyloid.”