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

D R Thal, I Sassin, C Schultz, C Haass, E Braak, H Braak

J Neuropathol Exp Neurol. 1999 Feb;58(2):210-6.

PMID: 10029103

Abstract:

The deposition of amyloid in the brain is a hallmark of Alzheimer disease (AD). Amyloid deposits consist of accumulations of beta-amyloid (Abeta), which is a 39-43 amino-acid peptide cleaved from the Abeta-protein precursor (APP). Another cleavage product of APP is the P3-peptide, which consists of the amino acids 17-42 of the Abeta-peptide. In order to study the deposition of N-terminal truncated forms of Abeta in the human entorhinal cortex, serial sections from 16 autopsy cases with AD-related pathology were immunostained with antibodies against Abeta1-40, Abeta1-42, Abeta17-23, and Abeta8-17, as well as with the Campbell-Switzer silver impregnation for amyloid. In the external entorhinal layers (pre-beta and pre-gamma), sharply delineated diffuse plaques were seen. They were labeled by silver impregnation and by all Abeta-antibodies used. By comparison, in the internal layers (pri-alpha, pri-beta, and pri-gamma) 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 Abeta17-23 and Abeta1-42 antibodies, but not with antibodies against Abeta8-17 and Abeta1-40. 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 Abeta1-42, probably representing the P3-peptide. These N-terminal truncated fragments of Abeta are capable of creating fine fibrillar "amyloid."

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248098 Amyloid β 17-42 human Amyloid β 17-42 human Price
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