The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Consequences of beta‐amyloid immunotherapy for Alzheimer's disease on neurons in the human cerebral cortex

Consequences of beta‐amyloid immunotherapy for Alzheimer's disease on neurons in the human cerebral cortex
Consequences of beta‐amyloid immunotherapy for Alzheimer's disease on neurons in the human cerebral cortex
Background: Alzheimer's disease (AD) patients in Aβ immunotherapy trials have demonstrated amyloid plaque removal but with little evidence of slowed cognitive decline. We have explored the consequences of immunotherapy on neuronal density and the morphology of neuronal processes.Methods:11 immunised AD patients (iAD) (Elan Pharmaceuticals, AN1792) were compared to 28 non‐immunised AD patients (cAD) as controls. Immunohistochemistry on sections of cortex from frontal, temporal and parietal lobes was performed for: neuron‐specific nuclear antigen (NeuN), neurofilament (NFP) and pPKR (phosphorylated pro‐apoptotic kinase detected in degenerating neurons). Status spongiosus (neuropil degeneration) was assessed in haematoxylin‐and eosin‐stained sections. We quantified NFP and pPKR labelling as load (%), the percentage area of cortex showing status spongiosus, NeuN‐positive neurons/field, curvature of the neuronal processes and interneuronal distance (m m). Data were corrected for age, gender, duration of dementia and APOE genotype.Results:Our data show in the iAD compared to the cAD cases: a significantly higher degree of spongiosus (53.3 vs 48.6, P = 0.013), fewer NeuN‐positive neurons/field (66.8 vs 73.7, P = 0.036), lower curvature of neuronal processes (1.13 vs 1.23, P < .001), a trends towards a lower pPKR load (0.08 vs 0.16, P = 0.070) and no‐significant change in mean interneuronal distance (713.6 vs 705.2, P = 0.370).Conclusions:After immunisation, there is evidence of enhanced neuronal damage in the form of exacerbated status spongiosus and a lower density of neurons. Remaining neurons seem “healthier” (less curvature of neuronal processes, less pPKR). The data raise the possibility that A β immunisation may accelerate the removal of neurons damaged by AD and are consistent with the report of increased cerebral atrophy detected with MRI.
1552-5260
P284
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Mouton-Liger, François
d653cf7c-8d35-421a-acaa-baeba71551d5
Nasser, Mariam
96bfbe05-1d76-4379-9b2a-1b8a99f829a2
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Gray, Françoise
d51d9569-90d8-4b13-8e36-4dc5372b50b5
Pickering, Ruth
4a828314-7ddf-4f96-abed-3407017d4c90
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Hugon, Jacques
de69c379-343f-42c5-ac70-0fb19eefd0bb
Paquet, Claire
4a54324b-6350-42e0-8343-3baa4a4ad53e
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Mouton-Liger, François
d653cf7c-8d35-421a-acaa-baeba71551d5
Nasser, Mariam
96bfbe05-1d76-4379-9b2a-1b8a99f829a2
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Gray, Françoise
d51d9569-90d8-4b13-8e36-4dc5372b50b5
Pickering, Ruth
4a828314-7ddf-4f96-abed-3407017d4c90
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Hugon, Jacques
de69c379-343f-42c5-ac70-0fb19eefd0bb
Paquet, Claire
4a54324b-6350-42e0-8343-3baa4a4ad53e

Boche, Delphine, Amin, Jay, Mouton-Liger, François, Nasser, Mariam, Love, Seth, Gray, Françoise, Pickering, Ruth, Nicoll, James, Holmes, Clive, Hugon, Jacques and Paquet, Claire (2013) Consequences of beta‐amyloid immunotherapy for Alzheimer's disease on neurons in the human cerebral cortex. Alzheimer's & Dementia, 9 (4S, Part 7), P284. (doi:10.1016/j.jalz.2013.05.571).

Record type: Meeting abstract

Abstract

Background: Alzheimer's disease (AD) patients in Aβ immunotherapy trials have demonstrated amyloid plaque removal but with little evidence of slowed cognitive decline. We have explored the consequences of immunotherapy on neuronal density and the morphology of neuronal processes.Methods:11 immunised AD patients (iAD) (Elan Pharmaceuticals, AN1792) were compared to 28 non‐immunised AD patients (cAD) as controls. Immunohistochemistry on sections of cortex from frontal, temporal and parietal lobes was performed for: neuron‐specific nuclear antigen (NeuN), neurofilament (NFP) and pPKR (phosphorylated pro‐apoptotic kinase detected in degenerating neurons). Status spongiosus (neuropil degeneration) was assessed in haematoxylin‐and eosin‐stained sections. We quantified NFP and pPKR labelling as load (%), the percentage area of cortex showing status spongiosus, NeuN‐positive neurons/field, curvature of the neuronal processes and interneuronal distance (m m). Data were corrected for age, gender, duration of dementia and APOE genotype.Results:Our data show in the iAD compared to the cAD cases: a significantly higher degree of spongiosus (53.3 vs 48.6, P = 0.013), fewer NeuN‐positive neurons/field (66.8 vs 73.7, P = 0.036), lower curvature of neuronal processes (1.13 vs 1.23, P < .001), a trends towards a lower pPKR load (0.08 vs 0.16, P = 0.070) and no‐significant change in mean interneuronal distance (713.6 vs 705.2, P = 0.370).Conclusions:After immunisation, there is evidence of enhanced neuronal damage in the form of exacerbated status spongiosus and a lower density of neurons. Remaining neurons seem “healthier” (less curvature of neuronal processes, less pPKR). The data raise the possibility that A β immunisation may accelerate the removal of neurons damaged by AD and are consistent with the report of increased cerebral atrophy detected with MRI.

This record has no associated files available for download.

More information

Published date: 1 July 2013

Identifiers

Local EPrints ID: 443621
URI: http://eprints.soton.ac.uk/id/eprint/443621
ISSN: 1552-5260
PURE UUID: 71a53941-b6e5-423a-b000-7f30b3960c20
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for Jay Amin: ORCID iD orcid.org/0000-0003-3792-0428
ORCID for James Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 04 Sep 2020 16:33
Last modified: 26 Nov 2021 03:03

Export record

Altmetrics

Contributors

Author: Delphine Boche ORCID iD
Author: Jay Amin ORCID iD
Author: François Mouton-Liger
Author: Mariam Nasser
Author: Seth Love
Author: Françoise Gray
Author: Ruth Pickering
Author: James Nicoll ORCID iD
Author: Clive Holmes ORCID iD
Author: Jacques Hugon
Author: Claire Paquet

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×