Cited by 1,397Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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

Nicoll, James A.R., Wilkinson, David, Holmes, Clive, Steart, Phil, Markham, Hannah, Weller, Roy O.·2003·Nature Medicine

Abstract

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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Crossref · 10.1038/nm840

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Authors
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O.
Affiliations
  • Southampton General Hospital (GB)
  • Moorgreen Hospital (GB)
Corresponding author
Nicoll, James A.R.
Venue
Nature Medicine
Published
2003-03-17
Volume
9
Issue
4
Pages
448-452
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2000917982
Cited by
1,397
References
14
Citations by year
2026: 16 · 2025: 17 · 2024: 24 · 2023: 24 · 2022: 32 · 2021: 32 · 2020: 32 · 2019: 41 · 2018: 25 · 2017: 39 · 2016: 46 · 2015: 48 · 2014: 68 · 2013: 70 · 2012: 58
FWCI
72.03
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, amyloid-beta immunotherapy, amyloid-beta, neuropathology, amyloid plaques, cerebral amyloid angiopathy, neurofibrillary tangles, neuropil threads, microglia, macrophage infiltration, plaque clearance
MeSH terms
Aged, Alzheimer Disease, Brain, Female, Humans, Meningoencephalitis, Peptide Fragments, Amyloid beta-Peptides, Alzheimer Vaccines

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