ISSN:
1432-0533
Keywords:
Key words Amyloid β-protein
;
Amyloid β-protein precursor
;
Astrocytes
;
Alzheimer’s disease
;
Fleecy amyloid
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The deposition of the amyloid β-protein (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). Aβ is a peptide consisting of 39–43 amino acids and is derived by β- and γ-secretase cleavage from the Aβ protein precursor (AβPP). An N-terminal-truncated form of Aβ can occur following α- and γ-secretase cleavage of AβPP. Fleecy amyloid is a recently identified distinct type of Aβ deposits occurring in the internal layers (pri-α, pri-β and pri-γ) of the human entorhinal cortex. Fleecy amyloid consists exclusively of N-terminal-truncated Aβ and is a transient form of Aβ deposits, which disappears in late-stage β-amyloidosis. In this study, the entorhinal cortex of 15 cases with AD-related pathology was used to examine astrocytes in the vicinity of N-terminal-truncated Aβ in fleecy amyloid of the layers pri-α, pri-β, and pri-γ in comparison to astrocytes in the vicinity of full-length Aβ in layers pre-β and pre-γ. Immunohistochemistry was performed with antibodies directed against AβPP, Aβ40, Aβ42, Aβ17–24, Aβ1–17 and Aβ8–17 as well as by double-labeling with antibodies directed against Aβ17–24, Aβ42, and glial fibrillary acid protein (GFAP). A large number of GFAP-positive astrocytes containing N-terminal-truncated Aβ fragments appeared in the vicinity of N-terminal-truncated Aβ, whereas Aβ-containing astrocytes were rarely seen in the vicinity of full-length Aβ. These results suggest that N-terminal-truncated Aβ peptide may be cleared preferentially from the extracellular space by astrocytic uptake and processing. Such an astroglial uptake of N-terminal-truncated Aβ may account for the transient nature of fleecy amyloid and point to the use of N-terminal truncation of Aβ in potential therapeutic strategies aimed at preventing the brain from amassing full-length Aβ deposits.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004010000242
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