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

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 & 2 others Julia R. Currie, David L. Miller

Research output: Contribution to journalArticle

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 α- 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.

Original languageEnglish (US)
Pages (from-to)389-402
Number of pages14
JournalActa Neuropathologica
Volume113
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

Fingerprint

A 17
Amyloidosis
Amyloid Precursor Protein Secretases
Neurons
Brain
Pathology
Amyloid Plaques
Carisoprodol
Down Syndrome
Amyloid
Mass Spectrometry
Alzheimer Disease
Western Blotting
Antibodies

Keywords

  • Alzheimer's disease
  • Down syndrome
  • Intraneuronal amyloid-β
  • Plaques
  • Tangles

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Wegiel, J., Kuchna, I., Nowicki, K., Frackowiak, J., Mazur-Kolecka, B., Imaki, H., ... Miller, D. L. (2007). Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration. Acta Neuropathologica, 113(4), 389-402. https://doi.org/10.1007/s00401-006-0191-4

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration. / Wegiel, Jerzy; Kuchna, Izabela; Nowicki, Krzysztof; Frackowiak, Janusz; Mazur-Kolecka, Bozena; Imaki, Humi; Wegiel, Jarek; Mehta, Pankaj D.; Silverman, Wayne P; Reisberg, Barry; deLeon, Mony; Wisniewski, Thomas; Pirttilla, Tuula; Frey, Harry; Lehtimäki, Terho; Kivimäki, Tarmo; Visser, Frank E.; Kamphorst, Wouter; Potempska, Anna; Bolton, David; Currie, Julia R.; Miller, David L.

In: Acta Neuropathologica, Vol. 113, No. 4, 04.2007, p. 389-402.

Research output: Contribution to journalArticle

Wegiel, J, Kuchna, I, Nowicki, K, Frackowiak, J, Mazur-Kolecka, B, Imaki, H, Wegiel, J, Mehta, PD, Silverman, WP, Reisberg, B, deLeon, M, Wisniewski, T, Pirttilla, T, Frey, H, Lehtimäki, T, Kivimäki, T, Visser, FE, Kamphorst, W, Potempska, A, Bolton, D, Currie, JR & Miller, DL 2007, 'Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration', Acta Neuropathologica, vol. 113, no. 4, pp. 389-402. https://doi.org/10.1007/s00401-006-0191-4
Wegiel, Jerzy ; Kuchna, Izabela ; Nowicki, Krzysztof ; Frackowiak, Janusz ; Mazur-Kolecka, Bozena ; Imaki, Humi ; Wegiel, Jarek ; Mehta, Pankaj D. ; Silverman, Wayne P ; Reisberg, Barry ; deLeon, Mony ; Wisniewski, Thomas ; Pirttilla, Tuula ; Frey, Harry ; Lehtimäki, Terho ; Kivimäki, Tarmo ; Visser, Frank E. ; Kamphorst, Wouter ; Potempska, Anna ; Bolton, David ; Currie, Julia R. ; Miller, David L. / Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration. In: Acta Neuropathologica. 2007 ; Vol. 113, No. 4. pp. 389-402.
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