Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis
Abstract
The amyloid cascade hypothesis of Alzheimer's disease (AD) is testable: it implies that interference with Abeta aggregation and plaque formation may be therapeutically useful. Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques. The first clinical studies of Abeta immunisation in AD patients (AN1792, Elan Pharmaceuticals) were halted when some patients suffered side effects. Since our confirmation that Abeta immunisation can prompt plaque removal in human AD, we have performed a clinical and neuropathological follow up of AD patients in the initial Elan Abeta immunisation trial. In immunised AD patients, we found: a lower Abeta load, with evidence that plaques had been removed; a reduced tau load in neuronal processes, but not in cell bodies; and no evidence of a beneficial effect on synapses. There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta. A pathophysiological mechanism involving effects on the cerebral vasculature is proposed for the clinical side effects observed with some active and passive vaccine protocols. Our current knowledge of the effects of Abeta immunotherapy is based on functional information from the early clinical trials and a few post mortem cases. Several further clinical studies are underway using a variety of protocols and important clinical, imaging and neuropathological data will become available in the near future. The information obtained will be important in helping to understand the pathogenesis not only of AD but also of other neurodegenerative disorders associated with protein aggregation.
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Amyloid removal is faster in patients with high baseline amyloid levels, which confounds direct comparison of anti-Aβ antibodies.
“There is also evidence that amyloid removal is faster in those patients with high baseline levels, further confounding a direct comparison of anti-Aβ antibodies 90 .”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [90]
Gantenerumab has an incidence of ARIA-E of 48%.
“| Gantenerumab | 13 1 | 42 b /27 | 67 | 52 | 2.5 | 48 b | 19.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [90]
Gantenerumab has a normalized rate of amyloid removal of 2.5 CL/4 wk/10mg/kg.
“| Gantenerumab | 13 1 | 42 b /27 | 67 | 52 | 2.5 | 48 b | 19.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [90]
Gantenerumab has an ARIA-E/amyloid removal rate index of 19.2.
“| Gantenerumab | 13 1 | 42 b /27 | 67 | 52 | 2.5 | 48 b | 19.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [90]
Gantenerumab removes 42 centiloids in 27 patients.
“| Gantenerumab | 13 1 | 42 b /27 | 67 | 52 | 2.5 | 48 b | 19.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [90]
In one human study, a vaccine to Aβ reduced plaque burden.
“In one human study, a vaccine to Aβ did reduce plaque burden, a remarkable technical achievement [248, 249].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [248]
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 [180]
There are multiple reasons why anti-Aβ clinical trials may have failed, including the late timing of the therapy.
“There are multiple reasons why these trials may have failed, including the late timing of the therapy. Thus, conclusions drawn from these trials may be premature (72, 73).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [72]
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The neuropathological diagnosis of Alzheimer's disease
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“Interestingly, immunization strategies targeting Aβ peptides may be useful in alleviating amyloid plaque burden, while shifting amyloid into CAA, sometimes associated with inflammation and hemorrhage [51, 52].”
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Microglial priming in neurodegenerative disease
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Self-citationTau-targeting therapies for Alzheimer disease
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“There does not appear to be a correlation between rate of amyloid removal and the incidence of ARIA-E, in contrast to what has previously been postulated 91 and as we will discuss below.”
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Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimers Disease
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“proinflammatory responses with increased microglial activation, cerebral amyloid angiopathy, and accumulation of soluble neurotoxic oligomeric A PP-A [271], may have adversely influenced the clinical course of AD.”
BackgroundAnimal Models of Alzheimer Disease
LaFerla, F. M., & Green, K. N. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006320 · Cited by 419 · see citing works
“Immunotherapy has progressed into numerous clinical trials and has been shown to reduce both Ab and tau levels in patients (Boche et al. 2010), as shown in mouse models (Schenk et al. 1999; Oddo et al. 2004).”
BackgroundAmyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics
Hampel, H., Elhage, A., Cho, M., Apostolova, L. G., Nicoll, J. A. R., & Atri, A. (2023) · Brain · doi:10.1093/brain/awad188 · Cited by 412 · see citing works
“45 Poorly understood mechanistic aspects include whether A β is transported to the vasculature in association with antibody (i.e. in the form of immune complexes) as a conjugate to apoli-poprotein E (APOE) or as unassociated soluble A β .”
BackgroundSelf-citationReview: sporadic cerebral amyloid angiopathy
Attems, J., Jellinger, K., Thal, D. R., & Van Nostrand, W. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01137.x · Cited by 371 · see citing works
Nelson, P. T., Head, E., Schmitt, F. A., Davis, P. R., Neltner, J. H., Jicha, G. A., Abner, E. L., Smith, C. D., Van Eldik, L. J., Kryscio, R. J., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0826-y · Cited by 365 · see citing works
“However, the limitations of the conclusions that can be drawn from the few autopsied anti-Ab immunotherapy cases have been acknowledged [34] and in fact some beneficial effects of the human immunotherapy studies have been seen in clinical trials [31, 35, 191, 202].”
Cognitive symptoms of Alzheimer’s disease: clinical management and prevention
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“Based on these fundamental observations, immunization of AD patients with synthetic full length Aβ42 (AN1792, Elan Pharmaceuticals) has been studied in a randomized, doubleblind, placebo-controlled phase 2a clinical trial [70,71].”
Immunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model
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“…trial, A plaque clearance had limited effect on tau pathology (Nicoll et al., 2003; Ferrer et al., 2004; Masliah et al., 2005a; Holmes et al., 2008; Boche et al., 2010a,b; Serrano-Pozo et al., 2010), which emphasizes the need for therapy that specifically targets this other major hallmark of the…”
BackgroundPiazza, F., Greenberg, S. M., Savoiardo, M., Gardinetti, M., Chiapparini, L., Raicher, I., Nitríni, R., Sakaguchi, H., Brioschi, M., Billo, G., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23857 · Cited by 237 · see citing works
“Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Ab autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.”
BackgroundEmerging Concepts in Alzheimer's Disease
Vinters, H. V. (2014) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163927 · Cited by 232 · see citing works
A review on advances of treatment modalities for Alzheimer's disease
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Nicoll, J. A. R., Buckland, G. R., Harrison, C. H., Page, A. M., Harris, S., Love, S., Neal, J., Holmes, C., & Boche, D. (2019) · Brain · doi:10.1093/brain/awz142 · Cited by 205 · see citing works
“The reduction in tau-containing plaque-associated dystrophic neurites is a striking consequence of immunization-mediated removal of amyloid-b from the cortex and has been described previously (Nicoll et al., 2003; Ferrer et al., 2004; Boche et al., 2010b).”
BackgroundResultInfluentialSelf-citationCongdon, E. E., Gu, J., Sait, H. B. R., & Sigurdsson, E. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.491001 · Cited by 195 · see citing works
“Although immunizationwas effective at reducing amyloid burden, there was no beneficial effect on synapses or clinical progression (8).”
BackgroundAPOE-ε2 and APOE-ε4 Correlate With Increased Amyloid Accumulation in Cerebral Vasculature
Nelson, P. T., Pious, N. M., Jicha, G. A., Wilcock, D. M., Fardo, D. W., Estus, S., & Rebeck, G. W. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31829a25b9 · Cited by 150 · see citing works
The transcription factor PU.1 is critical for viability and function of human brain microglia
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“In Alzheimer’s disease microglia may be helpful in clearing the brain of extracellular Ab42 deposits (Bard et al., 2000; Boche et al., 2010; Rogers et al., 2002).”
BackgroundProteinopathies, a core concept for understanding and ultimately treating degenerative disorders?
Bayer, T. A. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.03.007 · Cited by 141 · see citing works
The endocytic pathway in microglia during health, aging and Alzheimer’s disease
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BACE inhibition-dependent repair of Alzheimer’s pathophysiology
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“Admittedly, one conundrum in this interpretation is the appearance in several immunized patients of cortical patches lacking amyloid immediately adjacent to areas with considerable plaque accumulation (Nicoll et al., 2003; Boche et al., 2010).”
BackgroundPasquier, F., Sadowsky, C., Holstein, A. R., Prince, G. L., Peng, Y., Jackson, N. M., Fox, N. C., Ketter, N., Liu, E., Ryan, J. M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150376 · Cited by 105 · see citing works
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Using Pittsburgh Compound B for In Vivo PET Imaging of Fibrillar Amyloid-Beta
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“While Aβ immunization appears to be effective in reducing amyloid pathology in AD patients, this intervention has been observed to activate microglia reaction in the brain and it can result in severe side effects (Boche et al., 2010).”
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“Nonetheless the hypothesis remains dominant with the failures being interpreted as being related to either inadequate specificity (in the case of g-secretase inhibitors, resulting in off-target toxicity), unresponsive stage of disease, or neurovascular inflammation (as with the anti-Ab antibodies) [144].”
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“Brain uptake of IgG and other macromolecules may occur transcellularly or via ‘‘leaky’’ tight junctions (50, 51).”
Blood–brain barrier leakage and perivascular inflammation in cerebral amyloid angiopathy
Kozberg, M. G., Yi, I., Freeze, W. M., Auger, C. A., Scherlek, A. A., Greenberg, S. M., & van Veluw, S. J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac245 · Cited by 94 · see citing works
“These episodes are termed CAA-related inflammation (CAA-ri).7–9 In these cases, regions of inflammation have an increased CMB burden, suggesting that active inflammation may contribute to haemorrhage.10 Additionally, Pittsburgh compound B positron emission tomography imaging studies suggest that CAA-ri may involve Aβ…”
BackgroundXu, R., Wang, J., Xu, J., Song, X., Huang, H., Feng, Y., & Fu, C. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s236922 · Cited by 88 · see citing works
Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms
Greenberg, S. M., Bax, F., & van Veluw, S. J. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-024-01053-8 · Cited by 103 · see citing works
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“In addition, both active and passive immunotherapy increase the risk of adverse cerebral vascular events, including increased densities of cortical microhemorrhages and microvascular lesions, white matter abnormalities and vasogenic edema [103,108–112].”
BackgroundInnate Immunity in Alzheimer’s Disease: A Complex Affair
Guillot‐Sestier, M., & Town, T. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050008 · Cited by 71 · see citing works
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“However, as the exacerbation of concentric splitting after immunization occurs in the context of enhanced mobilization of plaque Aβ and its eventual perivascular clearance [4, 6, 31], we suggest that the ‘splitting’ may result from enhanced initial deposition of Aβ-apoE in the tunica media, associated with destruction…”
Self-citationAnimal models of cerebral amyloid angiopathy
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“clinical trials seem likely to be due largely to these changes in CAA (196, 197).”
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Immunotherapies for Alzheimer’s Disease—A Review
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“The exact mechanism of this was unknown and determined to have no clear relation to serum anti-Aβ42 antibody titers but may have been an autoimmune response rising from T cell interactions [85,86].”
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Review: Neuropathology and behavioural features of transgenic murine models of Alzheimer's disease
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“plaque load and increase microglial cell accumulation [33, 71–73].”
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“Reports on AD patients treated with Aβ immunization also indicate microglial contribution to Aβ clearance in human AD brains [42, 43].”
Backgroundp-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice
Walls, K. C., Ager, R. R., Vasilevko, V., Cheng, D., Medeiros, R., & LaFerla, F. M. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.05.047 · Cited by 58 · see citing works
Antibody-based therapy in Alzheimer's disease
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“Follow-up analyses of AD patients in the AN1792 trial revealed a reduced tau load in neuronal processes but not in the neuronal cell bodies [169].”
BackgroundAlzheimer disease neuropathology in a patient previously treated with aducanumab
Plowey, E. D., Bussière, T., Rajagovindan, R., Sebalusky, J., Hamann, S., von Hehn, C., Castrillo‐Viguera, C., Sandrock, A. W., Haeberlein, S. B., van Dyck, C. H., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02433-4 · Cited by 59 · see citing works
Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease
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tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β
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“…be beneficial in amyloidrelated imaging abnormalities, an adverse effect of anti-Ab immunotherapy (Sperling, 2011) characterized by perivascular inflammation, microhemorrhages, and edema attributed to the vascular effects of Ab released from amyloid plaques (Boche et al., 2010; Sakai et al., 2014).”
BackgroundMancini, S., Minniti, S., Gregori, M., Sancini, G., Cagnotto, A., Couraud, P., Ordóñez‐Gutiérrez, L., Wandosell, F. G., Salmona, M., & Re, F. (2015) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2015.09.003 · Cited by 54 · see citing works
Nanomedicine in Alzheimer's disease: Amyloid beta targeting strategy
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Alzheimer's Therapeutics: Translation of Preclinical Science to Clinical Drug Development
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“The most recent update on the neuropathology in cases from the original Phase I trial reports significant removal of Ab plaques and plaque-associated tau-positive dystrophic neurites but no differences between immunized and control AD cases in the density of phospho-tau-positive neuronal bodies (a marker for Braak Sta…”
BackgroundInfluentialPatterns of cerebral amyloid angiopathy define histopathological phenotypes in A lzheimer's disease
Allen, N., Robinson, A., Snowden, J. S., Davidson, Y. S., & Mann, D. M. A. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12070 · Cited by 49 · see citing works
Therapeutic targets of brain insulin resistance in sporadic Alzheimer's disease
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Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
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Recent developments with tau-based drug discovery
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“was, in fact, found to be effective in clearing the brain of the amyloid plaques but not neurofibrillary tangles [18].”
BackgroundP2Y receptors in Alzheimer's disease
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“The crucial role of microglia in controlling Aβ levels has been demonstrated in AD mouse models and AD patients where Aβ immunisation has been shown to decrease plaque load and increase microglial cell accumulation (Schenk et al., 1999; Nicoll et al., 2003; Boche et al., 2010).”
BackgroundBastard, N. L., Aerts, L., Sleegers, K., Martin, J., Broeckhoven, C. V., Deyn, P. P. D., & Engelborghs, S. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-110029 · Cited by 41 · see citing works
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Self-citationDantrolene, A Treatment for Alzheimer Disease?
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Nanoliposomes as a Therapeutic Tool for Alzheimer’s Disease
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“A complementary phase II trial was initiated in 2001, however, 6% of the immunized patients presented symptoms of aseptic meningoencephalitis, and the trial was terminated early in 2002 (Wisniewski and Frangione, 2005; Boche et al., 2010).”
BackgroundInvestigating Interventions in Alzheimer's Disease with Computer Simulation Models
Proctor, C. J., Boche, D., Gray, D. A., & Nicoll, J. A. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073631 · Cited by 38 · see citing works
“This intervention also predicts slightly lower levels of phospho-tau (compare green curves in Figure 2A and 2F) in agreement with neuropathological data [10].”
InfluentialSelf-citationCrane, A., Brubaker, W. D., Johansson, J. U., Trigunaite, A., Ceballos, J., Bradt, B. M., Glavis‐Bloom, C., Wallace, T. L., Tenner, A. J., & Rogers, J. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.04.015 · Cited by 34 · see citing works
“Although, as noted, these findings do not disallow CNS actions of Ab immunotherapy, they do strongly suggest that peripheral effects should be considered as well—particularly because peripheral strategies might avoid the CNS adverse effects that have been encountered in previous AD immunotherapy trials [1,4,5].”
BackgroundRoher, A. E., Cribbs, D. H., Kim, R. C., Maarouf, C. L., Whiteside, C. M., Kokjohn, T. A., Daugs, I. D., Head, E., Liebsack, C., Serrano, G. E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059735 · Cited by 34 · see citing works
Therapeutic Targeting of the Endoplasmic Reticulum in Alzheimers Disease
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“Over the past decade several therapeutic strategies, borne out of the amyloidogenic hypothesis of Alzheimer’s, have been developed that directly address Aβ aggregation [5], production [6] or clearance [7].”
BackgroundTobinick, E. L. (2012) · Current Alzheimer Research · doi:10.2174/156720512799015073 · Cited by 34 · see citing works
“edu treatment groups, including brain inflammation 1 , worsening cognition, or excess mortality [8,13-18].”
BackgroundAβ43 in human Alzheimer’s disease: effects of active Aβ42 immunization
Jäkel, L., Boche, D., Nicoll, J. A. R., & Verbeek, M. M. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0791-6 · Cited by 29 · see citing works
“Although this is a widely accepted method for relative protein quantification [6, 29, 30], a possible limitation of our study is that comparison of antigen load stained by different antibodies is not fully possible.”
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“The scientific harvest of this single clinical trial is listed in chronological order [1254–1286] (Thomson Reuters Pharma, update of August 24, 2012).”
BackgroundBouter, Y., Liekefeld, H., Pichlo, S., Westhoff, A. C., Fenn, L., Bakrania, P., & Bayer, T. A. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02418-3 · Cited by 25 · see citing works
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“This may strongly deplete extrasynaptic ACh levels and disturb the proper functional status of cholinoceptives microglia and/or astrocytes, endothelial, and smooth muscle cells comprising the main component of micro-blood vessels in the brain [75, 76].”
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Alzheimer’s Disease: Dawn of a New Era?
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“Phospho-tau analysis showed a reduction of aggregated tau in neuronal processes (44).”
BackgroundRoher, A. E., Maarouf, C. L., & Kokjohn, T. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150757 · Cited by 21 · see citing works
“In the AN-1792 clinical trials, neuropathology and neurochemical analyses hinted that the anti-A antibodies reached their targets [81–87].”
BackgroundPerspectives on the Tertiary Prevention Strategy for Alzheimer's Disease
Bu, X., Jiao, S., Lian, Y., & Wang, Y. (2015) · Current Alzheimer Research · doi:10.2174/1567205013666151215110114 · Cited by 20 · see citing works
“The first active Aβ vaccine AN1792 lowered brain Aβ plaques, but did not provide benefits in synaptic integrity or cognitive performance [11].”
BackgroundHarnessing the Immune System for Treatment and Detection of Tau Pathology
Congdon, E. E., Krishnaswamy, S., & Sigurdsson, E. M. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132435 · Cited by 20 · see citing works
“In a Phase II Bapineuzumab trial, significant decrease in phospho-tau was detected in treated individuals [10, 21].”
Scherlek, A. A., Kozberg, M. G., Nicoll, J. A. R., Perosa, V., Freeze, W. M., van der Weerd, L., Bacskai, B. J., Greenberg, S. M., Frosch, M. P., Boche, D., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac021 · Cited by 20 · see citing works
“This observation is detected with the addition of cases with longer post-immunization survival times and thus could reflect that the response to ongoing neurodegenerative processes, such as tau pathology, is still progressing.(3,13) Future studies are needed to determine the nature of these neuroinflammatory responses.”
Self-citationAMBAR, an Encouraging Alzheimer's Trial That Raises Questions
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Alzheimer Disease and Cellular Mechanisms of Memory Storage
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“Unfortunately, these trials did not yield anticipated positive results (32, 33).”
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“Therefore passive immunization has become a valuable alternative [44, 45].”
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“impairments [7–9], and the same was observed in human beings [10].”
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“…Aβ to blood vessels based on one of the postulated mechanisms for amyloid plaque clearance by Aβ immunotherapy, which states that anti-Aβ antibodies directly interact with amyloid plaques, resulting in disaggregation and solubilization of Aβ fibrils (Bacskai et al., 2002; Boche et al., 2010).”
Effects of Microglial Cytokines on Alzheimer’s Disease-Related Phenomena
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“Indeed, although a clear correlation between the level of antibody production and the extent of plaque clearance was obtained in the Elan AN-1792 clinical trial, some cases demonstrated no profound plaque clearance regardless of Aβ antibody production (Boche et al., 2010), suggesting that either Aβ antibody titers wer…”
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“…behind ARIA is suspected to involve the antibody-mediated breakdown of neuritic plaques, resulting in the release of Aβ and its deposition within vessels; this leads to CAA, perivascular inflammation, and compromised Aβ clearance (3), thereby indicating a potential connection between CAA and ARIA.”
- Authors
- Boche, D., Denham, N., Holmes, C., & Nicoll, J. A. R.
- Affiliations
- Southampton General Hospital (GB)
- Corresponding author
- Boche, Delphine
- Venue
- Acta Neuropathologica
- Published
- 2010-07-15
- Volume
- 120
- Issue
- 3
- Pages
- 369-384
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2077023014
- Cited by
- 135
- References
- 132
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 1 · 2020: 8 · 2019: 12 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 5 · 2014: 15 · 2013: 19 · 2012: 15
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- 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, amyloid-beta immunotherapy, amyloid-beta 42, amyloid hypothesis, amyloid plaques, tau pathology, microglial activation, cerebral amyloid angiopathy, cerebral vasculature, vaccine side effects, amyloid precursor protein transgenic mice, Alzheimer's disease pathogenesis
- MeSH terms
- Alzheimer Disease, Animals, Brain, Clinical Trials as Topic, Humans, Peptide Fragments, Amyloid beta-Peptides, Immunotherapy, Active, Alzheimer Vaccines, Mice
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