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Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report

Record type: Article

Amyloid-beta peptide (Abeta) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment. Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)-(iii) strongly resemble the changes seen after Abeta immunotherapy in mouse models of AD and suggest that the immune response generated against the peptide elicited clearance of Abeta plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7-9).

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Citation

Nicoll, James A.R., Wilkinson, David, Holmes, Clive, Steart, Phil, Markham, Hannah and Weller, Roy O. (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report Nature Medicine, 9, (4), pp. 448-452. (doi:10.1038/nm840).

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Published date: 2003

Identifiers

Local EPrints ID: 27673
URI: http://eprints.soton.ac.uk/id/eprint/27673
ISSN: 1078-8956
PURE UUID: b2abfebe-82bc-47af-9451-a10afb75bd68
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 26 Apr 2006
Last modified: 17 Jul 2017 16:04

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Contributors

Author: David Wilkinson
Author: Clive Holmes
Author: Phil Steart
Author: Hannah Markham
Author: Roy O. Weller

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