Long-term effects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial

@article{Holmes2008LongtermEO,
  title={Long-term effects of A$\beta$42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial},
  author={Clive Holmes and Delphine Boche and David George Wilkinson and Ghasem Yadegarfar and Vivienne Hopkins and Anthony J. Bayer and Roy W Jones and Roger Alan Bullock and Seth Love and James W. Neal and Elina Zotova and James A R Nicoll},
  journal={The Lancet},
  year={2008},
  volume={372},
  pages={216-223}
}
BACKGROUND Immunisation of patients with Alzheimer's disease with full-length amyloid-beta peptide (Abeta(42)) can clear amyloid plaques from the brain. Our aim was to assess the relation between Abeta(42) immune response, degree of plaque removal, and long-term clinical outcomes. METHODS In June, 2003, consent for long-term clinical follow-up, post-mortem neuropathological examination, or both, was sought from 80 patients (or their carers) who had entered a phase I randomised, placebo… 
Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis
TLDR
It is confirmed that Aβ immunisation can prompt plaque removal in human AD and a pathophysiological mechanism involving effects on the cerebral vasculature is proposed for the clinical side effects observed with some active and passive vaccine protocols.
Effect of active Aβ immunotherapy on neurons in human Alzheimer's disease
TLDR
The findings suggest that in established AD this form of active Aβ immunization may predominantly accelerate loss of damaged degenerating neurons, consistent with in vivo imaging indicating an increased rate of cerebral atrophy in immunized AD patients.
Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study
TLDR
The findings suggest that CAD106 has a favourable safety profile and acceptable antibody response in patients with Alzheimer's disease.
Amyloid-β Immunotherapy for Alzheimers Disease
TLDR
Signs of cognitive stabilization and apparent plaque clearance were obtained in subset of patients who generated antibody titers and promising preliminary data support further efforts to refine Aβ immunotherapy to produce highly effective and safer active and passive vaccines for AD.
Reduction of amyloid beta-peptide accumulation in Tg2576 transgenic mice by oral vaccination.
TLDR
Results suggest this edible vehicle for Abeta vaccination has a potential clinical application in the treatment of AD, and anti-Abeta antibodies were effectively induced after oral immunization.
Disease-Modifying Approach to the Treatment of Alzheimer’s Disease
TLDR
Compounds that stimulate α-secretase, the enzyme responsible for non-amyloidogenic metabolism of APP, are being developed and one of these, EHT-0202, has recently commenced evaluation in a phase II study, and compounds that inhibit γ-secret enzyme, the pivotal enzyme that generates Aβ, have been identified.
Consequence of Abeta immunization on the vasculature of human Alzheimer's disease brain.
TLDR
The findings are consistent with the hypothesis that Abeta immunization results in solubilization of plaque Abeta42 which, at least in part, exits the brain via the perivascular pathway, causing a transient increase in the severity of CAA.
Aβ43 in human Alzheimer’s disease: effects of active Aβ42 immunization
TLDR
It is shown by using immunohistochemistry that in unimmunized AD patients Aβ43 is a frequent constituent of plaques, similar to Aβ42 (3.9% immunostained area), and that A β43 is cleared from plaques after Aβ immunotherapy,Similar to A β42 and Aβ40.
Amyloid-β immunisation for Alzheimer's disease
TLDR
Two new approaches to active and passive immunotherapy are under investigation in clinical trials with the aim of producing safe methods for immunological therapy and prevention of Alzheimer's disease.
Aβ immunotherapy for Alzheimer’s disease: effects on apoE and cerebral vasculopathy
TLDR
The findings suggest that apoE is involved in the removal of plaques and transport of Aβ to the cerebral vasculature induced by Aβ immunotherapy.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial
TLDR
This phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis provides an indication that Aβ immunotherapy may be useful in Alzheimer disease.
Antibodies against β-Amyloid Slow Cognitive Decline in Alzheimer's Disease
To test whether antibodies against beta-amyloid are effective in slowing progression of Alzheimer's disease, we assessed cognitive functions in 30 patients who received a prime and a booster
Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease.
TLDR
It is established that antibodies against beta-amyloid plaques can slow cognitive decline in patients with Alzheimer's disease.
Absence of β-amyloid deposits after immunization in Alzheimer disease with lewy body dementia
TLDR
In this Lewy body variant case, with globally stable functional and cognitive features, Aβ immunization resulted in a significant clearance of amyloid deposits, with remaining tau and synuclein pathological features in the brain.
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
TLDR
It is suggested that the immune response generated against the peptide elicited clearance of Aβ plaques in this patient and strongly resemble the changes seen after Aβ immunotherapy in mouse models of AD.
Absence of beta-amyloid deposits after immunization in Alzheimer disease with Lewy body dementia.
TLDR
In this Lewy body variant case, with globally stable functional and cognitive features, Abeta immunization resulted in a significant clearance of amyloid deposits, with remaining tau and synuclein pathological features in the brain.
Two-year follow-up of amyloid deposition in patients with Alzheimer's disease.
TLDR
Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer’s disease and therefore may precede a decline in rCMRGlc and cognition.
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
TLDR
It is reported that immunization of the young animals essentially prevented the development of β-amyloid-plaque formation, neuritic dystrophy and astrogliosis, and treatment of the older animals markedly reduced the extent and progression of these AD-like neuropathologies.
Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease.
TLDR
The occurrence of intrinsic T cell reactivity to the self-antigen Abeta in humans has implications for the design of Abeta vaccines, may itself be linked to AD susceptibility and course, and appears to be associated with the aging process.
Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization
TLDR
Postvaccination meningoencephalitis occurred without clear relation to serum anti-Aβ42 antibody titers and potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti- Aβ immunotherapy for AD.
...
1
2
3
4
...