Dr. Thal et al., Fleecy amyloid deposits in the internal layers of the human entorhinal cortex are comprised of N-terminal truncated fragments of A beta, J NE EXP NE, 58(2), 1999, pp. 210-216
Citations number
25
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
The deposition of amyloid in the brain is a hallmark of Alzheimer disease (
AD). Amyloid deposits consist of accumulations of beta-amyloid (A beta), wh
ich is a 39-43 amino-acid peptide cleaved from the A beta-protein precursor
(APP). Another cleavage product of APP is the P3-peptide, which consists o
f the amino acids 17-42 of the A beta-peptide. In order to study the deposi
tion of N-terminal truncated forms of A beta in the human entorhinal cortex
, serial sections from 16 autopsy cases with AD-related pathology were immu
nostained with antibodies against A beta(1-40), A beta(1-42), A beta(17-23)
, and A beta(8-17), as well as with the Campbell-Switzer silver impregnatio
n for amyloid. In the external entorhinal layers (pre-beta and pre-gamma),
sharply delineated diffuse plaques were seen. They were labeled by silver i
mpregnation and by all A beta-antibodies used. By comparison, in the intern
al layers (pri-alpha, pri-beta, and pri-gamma) blurred, ill-defined clouds
of amyloid existed, in addition to sharply delineated diffuse plaques. Thes
e clouds of amyloid were termed "fleecy amyloid." Immunohistochemically, fl
eecy amyloid was stained by A beta(17-23) and A beta(1-42) antibodies, but
not with antibodies against A beta(8-17) and A beta(1-40). Using the Campbe
ll-Switzer technique, the fleecy amyloid deposits were found to be fine arg
yrophilic amyloid fibrils. Thus, the internal entorhinal layers are suscept
ible to a distinct type of amyloid, namely fleecy amyloid. This fleecy amyl
oid obviously corresponds to N-terminal truncated fragments of A beta(1-42)
, probably representing the P3-peptide. These N-terminal truncated fragment
s of A beta are capable of creating fine fibrillar "amyloid.".