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Acta Neuropathologica
Published in: Acta Neuropathologica 4/2007

Open Access 01-04-2007 | Original Paper

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration

Authors: Jerzy Wegiel, Izabela Kuchna, Krzysztof Nowicki, Janusz Frackowiak, Bozena Mazur-Kolecka, Humi Imaki, Jarek Wegiel, Pankaj D. Mehta, Wayne P. Silverman, Barry Reisberg, Mony deLeon, Thomas Wisniewski, Tuula Pirttilla, Harry Frey, Terho Lehtimäki, Tarmo Kivimäki, Frank E. Visser, Wouter Kamphorst, Anna Potempska, David Bolton, Julia R. Currie, David L. Miller

Published in: Acta Neuropathologica | Issue 4/2007

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Abstract

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ17–40/42). The presence of N-terminally truncated Aβ17–40 and Aβ17–42 in the control brains was confirmed by Western blotting and the identity of Aβ17–40 was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ17–42 immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism.
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Metadata
Title
Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration
Authors
Jerzy Wegiel
Izabela Kuchna
Krzysztof Nowicki
Janusz Frackowiak
Bozena Mazur-Kolecka
Humi Imaki
Jarek Wegiel
Pankaj D. Mehta
Wayne P. Silverman
Barry Reisberg
Mony deLeon
Thomas Wisniewski
Tuula Pirttilla
Harry Frey
Terho Lehtimäki
Tarmo Kivimäki
Frank E. Visser
Wouter Kamphorst
Anna Potempska
David Bolton
Julia R. Currie
David L. Miller
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 4/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-006-0191-4

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