Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and tau pathology
Open accessAbstract
Anti-amyloid-beta immunization leads to amyloid clearance in patients with Alzheimer's disease, but the effect of vaccination on amyloid-beta-induced neuronal pathology has not been quantitatively examined. The objectives of this study were to address the effects of anti-amyloid-beta active immunization on neurite trajectories and the pathological hallmarks of Alzheimer's disease in the human hippocampus. Hippocampal sections from five patients with Alzheimer's disease enrolled in the AN1792 Phase 2a trial were compared with those from 13 non-immunized Braak-stage and age-matched patients with Alzheimer's disease, and eight age-matched non-demented controls. Analyses included neurite curvature ratio as a quantitative measure of neuritic abnormalities, amyloid and tau loads, and a quantitative characterization of plaque-associated neuritic dystrophy and astrocytosis. Amyloid load and density of dense-core plaques were decreased in the immunized group compared to non-immunized patients (P < 0.01 and P < 0.001, respectively). The curvature ratio in non-immunized patients with Alzheimer's disease was elevated compared to non-demented controls (P < 0.0001). In immunized patients, however, the curvature ratio was normalized when compared to non-immunized patients (P < 0.0001), and not different from non-demented controls. In the non-immunized patients, neurites close to dense-core plaques (within 50 microm) were more abnormal than those far from plaques (i.e. beyond 50 microm) (P < 0.0001). By contrast, in the immunized group neurites close to and far from the remaining dense-core plaques did not differ, and both were straighter compared to the non-immunized patients (P < 0.0001). Compared to non-immunized patients, dense-core plaques remaining after immunization had similar degree of astrocytosis (P = 0.6060), more embedded dystrophic neurites (P < 0.0001) and were more likely to have mitochondrial accumulation (P < 0.001). In addition, there was a significant decrease in the density of paired helical filament-1-positive neurons in the immunized group as compared to the non-immunized (P < 0.05), but not in the density of Alz50 or thioflavin-S positive tangles, suggesting a modest effect of anti-amyloid-beta immunization on tangle pathology. Clearance of amyloid plaques upon immunization with AN1792 effectively improves a morphological measure of neurite abnormality in the hippocampus. This improvement is not just attributable to the decrease in plaque load, but also occurs within the halo of the remaining dense-core plaques. However, these remaining plaques still retain some of their toxic potential. Anti-amyloid-beta immunization might also ameliorate the hippocampal tau pathology through a decrease in tau phosphorylation. These data agree with preclinical animal studies and further demonstrate that human anti-amyloid-beta immunization does not merely clear amyloid from the Alzheimer's disease brain, but reduces some of the neuronal alterations that characterize Alzheimer's disease.
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In the first active immunization trial, the AN-1792 vaccine seemed to show some ability to clear Aβ plaque-associated tau lesions through plaque removal.
“In the first active immunization trial, the AN-1792 vaccine seemed to show some ability to clear Aβ plaque-associated tau lesions through plaque removal179–181”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [179]
There have been hints of some beneficial effects (clinical and biochemical) linked to human anti-Aβ immunotherapies.
“In fact, there have been hints of some beneficial effects (clinical and biochemical) linked to human anti-Aβ immunotherapies (74-79).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [74]
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- Authors
- Serrano-Pozo, A., William, C. M., Ferrer, I., Uro-Coste, E., Delisle, M.-B., Maurage, C.-A., Hock, C., Nitsch, R. M., Masliah, E., Growdon, J. H., Frosch, M. P., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Inserm (FR)
- University of Zurich (CH)
- University of California San Diego (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-03-31
- Volume
- 133
- Issue
- 5
- Pages
- 1312-1327
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2859150
- OpenAlex
- W1985613394
- Cited by
- 159
- References
- 54
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 9 · 2023: 5 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 12 · 2015: 12 · 2014: 18 · 2013: 16 · 2012: 17
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute on Aging (AG-08487, R01AG008487, P50AG005134)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neurite morphology, tau pathology, amyloid plaques, dystrophic neurites, astrocyte activation, paired helical filaments, hippocampus, amyloid clearance, mitochondrial accumulation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Antibodies, Monoclonal, Astrocytes, Female, Gliosis, Hippocampus, Humans, Immunohistochemistry, Male, Neurons, Phosphorylation, Vaccination, Amyloid beta-Peptides, Neurites, Neurofibrillary Tangles, tau Proteins, Protein Folding, Voltage-Dependent Anion Channel 1, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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