Amyloid Beta annular protofibrils in cell processes and synapses accumulate with aging and Alzheimer-associated genetic modification.
Amyloid beta (Abeta) annular protofibrils (APFs) have been described where the structure is related to that of beta barrel pore-forming bacterial toxins and exhibits cellular toxicity. To investigate the relationship of Abeta APFs to disease and their ultrastructural localization in brain tissue, we conducted a pre-embedding immunoelectron microscopic study using anti-annular protofibril antiserum. We examined brain tissues of young- and old-aged amyloid precursor protein transgenic mice (APP23), neprilysin knockout APP23 mice, and nontransgenic littermates. alphaAPF-immunoreactions tended to be found (1) on plasma membranes and vesicles inside of cell processes, but not on amyloid fibrils, (2) with higher density due to aging, APP transgene, and neprilysin deficiency, and (3) with higher positive rate at synaptic compartments in aged APP23, especially in neprilysin knockout APP23 mice. These findings imply that APFs are distinct from amyloid fibrils, interact with biological membranes, and might be related to synaptic dysfunction in Alzheimer model mouse brains.
Kokubo
Hideko
H
School of Health Sciences, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8514, Japan.
Kayed
Rakez
R
Glabe
Charles G
CG
Staufenbiel
Matthias
M
Saido
Takaomi C
TC
Iwata
Nobuhisa
N
Yamaguchi
Haruyasu
H
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