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Aβ43 in human Alzheimer's disease: effects of active Aβ42 immunization

Aβ43 in human Alzheimer's disease: effects of active Aβ42 immunization
Aβ43 in human Alzheimer's disease: effects of active Aβ42 immunization

Neuropathological follow-up of patients with Alzheimer's disease (AD) who participated in the first clinical trial of Amyloid-β 42 (Aβ42) immunization (AN1792, Elan Pharmaceuticals) has shown that immunization can induce removal of Aβ42 and Aβ40 from plaques, whereas analysis of the cerebral vessels has shown increased levels of these Aβ peptides in cerebral amyloid angiopathy (CAA). Aβ43 has been less frequently studied in AD, but its aggregation propensity and neurotoxic properties suggest it may have an important pathogenic role. In the current study we show by using immunohistochemistry that in unimmunized AD patients Aβ43 is a frequent constituent of plaques (6.0% immunostained area), similar to Aβ42 (3.9% immunostained area). Aβ43 immunostained area was significantly higher than that of Aβ40 (2.3%, p = 0.006). In addition, we show that Aβ43 is only a minor component of CAA in both parenchymal vessels (1.5 Aβ43-positive vessels per cm2 cortex vs. 5.3 Aβ42-positive vessels, p = 0.03, and 6.2 Aβ40-positive vessels, p = 0.045) and leptomeningeal vessels (5.6% Aβ43-positive vessels vs. 17.3% Aβ42-positive vessels, p = 0.007, and 27.4% Aβ40-positive vessels, p = 0.003). Furthermore, we have shown that Aβ43 is cleared from plaques after Aβ immunotherapy, similar to Aβ42 and Aβ40. Cerebrovascular Aβ43 levels did not change after immunotherapy.

Alzheimer’s disease, Amyloid-β, Aβ immunotherapy, Aβ43, Cerebral amyloid angiopathy, Human study, Immunohistochemistry
2051-5960
1-11
Jäkel, Lieke
c502334c-8521-4a72-a75e-8ee4105e9ee7
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Verbeek, Marcel M.
c21991ca-081f-4249-9c88-ba1a94b58b3f
Jäkel, Lieke
c502334c-8521-4a72-a75e-8ee4105e9ee7
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Verbeek, Marcel M.
c21991ca-081f-4249-9c88-ba1a94b58b3f

Jäkel, Lieke, Boche, Delphine, Nicoll, James A.R. and Verbeek, Marcel M. (2019) Aβ43 in human Alzheimer's disease: effects of active Aβ42 immunization. Acta Neuropathologica Communications, 7 (1), 1-11. (doi:10.1186/s40478-019-0791-6).

Record type: Article

Abstract

Neuropathological follow-up of patients with Alzheimer's disease (AD) who participated in the first clinical trial of Amyloid-β 42 (Aβ42) immunization (AN1792, Elan Pharmaceuticals) has shown that immunization can induce removal of Aβ42 and Aβ40 from plaques, whereas analysis of the cerebral vessels has shown increased levels of these Aβ peptides in cerebral amyloid angiopathy (CAA). Aβ43 has been less frequently studied in AD, but its aggregation propensity and neurotoxic properties suggest it may have an important pathogenic role. In the current study we show by using immunohistochemistry that in unimmunized AD patients Aβ43 is a frequent constituent of plaques (6.0% immunostained area), similar to Aβ42 (3.9% immunostained area). Aβ43 immunostained area was significantly higher than that of Aβ40 (2.3%, p = 0.006). In addition, we show that Aβ43 is only a minor component of CAA in both parenchymal vessels (1.5 Aβ43-positive vessels per cm2 cortex vs. 5.3 Aβ42-positive vessels, p = 0.03, and 6.2 Aβ40-positive vessels, p = 0.045) and leptomeningeal vessels (5.6% Aβ43-positive vessels vs. 17.3% Aβ42-positive vessels, p = 0.007, and 27.4% Aβ40-positive vessels, p = 0.003). Furthermore, we have shown that Aβ43 is cleared from plaques after Aβ immunotherapy, similar to Aβ42 and Aβ40. Cerebrovascular Aβ43 levels did not change after immunotherapy.

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Accepted/In Press date: 15 August 2019
Published date: 2 September 2019
Keywords: Alzheimer’s disease, Amyloid-β, Aβ immunotherapy, Aβ43, Cerebral amyloid angiopathy, Human study, Immunohistochemistry

Identifiers

Local EPrints ID: 434526
URI: https://eprints.soton.ac.uk/id/eprint/434526
ISSN: 2051-5960
PURE UUID: 433abf97-bcef-4bd1-a40f-02c8363d0ccd
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 27 Sep 2019 16:30
Last modified: 15 Oct 2019 00:48

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Contributors

Author: Lieke Jäkel
Author: Delphine Boche ORCID iD
Author: Marcel M. Verbeek

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