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Reduction of aggregated Tau in neuronal processes but not in the cell bodies after AB42 immunisation in Alzheimer’s disease

Reduction of aggregated Tau in neuronal processes but not in the cell bodies after AB42 immunisation in Alzheimer’s disease
Reduction of aggregated Tau in neuronal processes but not in the cell bodies after AB42 immunisation in Alzheimer’s disease
Alzheimer’s disease (AD) pathology is characterised by aggregation in the brain of amyloid-? (A?) peptide and hyperphosphorylated tau (phospho-tau), although how these proteins interact in disease pathogenesis is unclear. A? immunisation results in removal of A? from the brain but cognitive decline continues to progress, possibly due to persistent phospho-tau. We quantified phospho-tau and A?42 in the brains of 10 AD patients (iAD) who were actively immunised with A?42 (AN1792, Elan Pharmaceuticals) compared with 28 unimmunised AD cases (cAD). The phospho-tau load was lower in the iAD than the cAD group in the cerebral cortex (cAD 1.08% vs. iAD 0.72%, P = 0.048), CA1 hippocampus (cAD 2.26% vs. iAD 1.05%; P = 0.001), subiculum (cAD 1.60% vs. iAD 0.31%; P = 0.001) and entorhinal cortex (cAD 1.10% vs. iAD 0.18%; P < 0.001). Assessment of the localisation within neurons of phospho-tau indicated that the A? immunotherapy-associated reduction was confined to neuronal processes, i.e. neuropil threads and dystrophic neurites. However, the phospho-tau accumulation in the neuronal cell bodies, contributing to neurofibrillary tangles, appeared not to be affected. In showing that A? immunisation can influence phospho-tau pathology, we confirm the position of A? as a target for modifying tau accumulation in AD and demonstrate a link between these proteins. However, the continuing progression of cognitive decline in AD patients after A? immunisation may be explained by its lack of apparent effect on tangles.
alzheimer’s disease, tau, immunisation, amyloid
1432-0533
13-20
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Donald, Jane
238881f4-d4e0-4627-951e-5214996e6ecc
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Harris, Scott
19ea097b-df15-4f0f-be19-8ac42c190028
Neal, James W.
12d0ba0f-b29d-43ca-8e61-af46a430367b
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Donald, Jane
238881f4-d4e0-4627-951e-5214996e6ecc
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Harris, Scott
19ea097b-df15-4f0f-be19-8ac42c190028
Neal, James W.
12d0ba0f-b29d-43ca-8e61-af46a430367b
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed

Boche, Delphine, Donald, Jane, Love, Seth, Harris, Scott, Neal, James W., Holmes, C. and Nicoll, James A.R. (2010) Reduction of aggregated Tau in neuronal processes but not in the cell bodies after AB42 immunisation in Alzheimer’s disease. Acta Neuropathologica, 120 (1), 13-20. (doi:10.1007/s00401-010-0705-y).

Record type: Article

Abstract

Alzheimer’s disease (AD) pathology is characterised by aggregation in the brain of amyloid-? (A?) peptide and hyperphosphorylated tau (phospho-tau), although how these proteins interact in disease pathogenesis is unclear. A? immunisation results in removal of A? from the brain but cognitive decline continues to progress, possibly due to persistent phospho-tau. We quantified phospho-tau and A?42 in the brains of 10 AD patients (iAD) who were actively immunised with A?42 (AN1792, Elan Pharmaceuticals) compared with 28 unimmunised AD cases (cAD). The phospho-tau load was lower in the iAD than the cAD group in the cerebral cortex (cAD 1.08% vs. iAD 0.72%, P = 0.048), CA1 hippocampus (cAD 2.26% vs. iAD 1.05%; P = 0.001), subiculum (cAD 1.60% vs. iAD 0.31%; P = 0.001) and entorhinal cortex (cAD 1.10% vs. iAD 0.18%; P < 0.001). Assessment of the localisation within neurons of phospho-tau indicated that the A? immunotherapy-associated reduction was confined to neuronal processes, i.e. neuropil threads and dystrophic neurites. However, the phospho-tau accumulation in the neuronal cell bodies, contributing to neurofibrillary tangles, appeared not to be affected. In showing that A? immunisation can influence phospho-tau pathology, we confirm the position of A? as a target for modifying tau accumulation in AD and demonstrate a link between these proteins. However, the continuing progression of cognitive decline in AD patients after A? immunisation may be explained by its lack of apparent effect on tangles.

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Published date: July 2010
Keywords: alzheimer’s disease, tau, immunisation, amyloid
Organisations: Community Clinical Sciences

Identifiers

Local EPrints ID: 158119
URI: https://eprints.soton.ac.uk/id/eprint/158119
ISSN: 1432-0533
PURE UUID: 3f8f9782-5fbc-4bb5-985d-a4acb88e0051
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for C. Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 15 Jun 2010 12:49
Last modified: 20 Jul 2019 01:09

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