Skip to main content Accessibility help
×
Home

Article contents

Current State of Immunotherapy for Alzheimer’s Disease

Published online by Cambridge University Press:  07 November 2014

Norman R. Relkin
Affiliation:
Dr. Relkin is director of the Weill Cornell Memory Disorders Program at, Weill Cornell Medical College, in New York

Extract

There are currently over two dozen agents targeting β-amyloid (Aβ) in human clinical trials. More than a dozen of these are forms of anti-amyloid immunotherapy. Although other anti-amyloid interventions are further along in the development process, thus far only immunotherapy has provided post-mortem evidence that it can alter elements of the underlying pathology of Alzheimer’s disease (AD) in actual patients.

In the past 30 years, there have been many attempts to develop treatments for AD. Early therapies were developed based on a limited understanding of the disease (Slide 1). Prior to the 1980s, a clear pathophysiologic mechanism for AD was not known; instead, symptomatic therapies targeted associated symptoms, such as agitation, insomnia, and psychosis. In the 1970s, several preclinical studies pointed toward synaptic transmission abnormalities, particularly neurochemical abnormalities, as the root cause of AD, and treatments with cholinesterase inhibitors grew out of that theory. Today, the cholinergic hypothesis has been largely discredited in the primary pathogenesis of AD. Another theory based on neurotransmitter abnormalities, the glutaminergic hypothesis, has also gone out of favor as a causal explanation for AD. This did not stop medications based on these mechanisms from finding a meaningful place in the clinical pharmacopeia for treatment of AD.

In the 1990s, many clinical trials followed up on epidemiologic studies suggesting systemic causes of AD. These clinical trials focused on anti-inflammatories, hormone replacement, and antioxidants. The trials performed have largely failed, with the possible exception of the trials of vitamin E, an antioxidant. None of these agents have proven useful as disease-modifying therapies for symptomatic AD.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below.

References

1.Zagorski, MG, Yang, J, Shao, H, Ma, K, Zeng, H, Hong, A. Methodological and chemical factors affecting amyloid beta peptide amyloidogenicity. Methods Enzymol. 1999;309:189204.CrossRefGoogle ScholarPubMed
2.Hilbich, C, Kisters-Woike, B, Reed, J, Masters, CL, Beyreuther, K. Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer’s disease. J Mol Biol. 1991;218:149163.CrossRefGoogle Scholar
3.Weksler, ME, Gouras, G, Relkin, NR, Szabo, P. The immune system, amyloid-beta peptide, and Alzheimer’s disease. Immunol Rev. 2005;205:244256.CrossRefGoogle ScholarPubMed
4.Zlokovic, BV. Clearing amyloid through the blood-brain barrier. J Neurochem. 2004; 89(4): 807811.CrossRefGoogle Scholar
5.Schenk, D, Barbour, R, Dunn, W, et al.Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999; 400(6740): 173177.CrossRefGoogle Scholar
6.Morgan, D, Diamond, DM, Gottschall, PE, et al.A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature. 2000; 408(6815): 982985.CrossRefGoogle Scholar
7.Nicoll, JA, Wilkinson, D, Holmes, C, Steart, P, Markham, H, Weller, RO. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med. 2003; 9(4): 448452.CrossRefGoogle Scholar
8.Lombardo, JA, Stern, EA, McLellan, ME, et al.Amyloid-beta antibody treatment leads to rapid normalization of plaque-induced neuritic alterations. J Neurosci. 2003; 23(34): 1087910883.Google Scholar
9.Pfeifer, M, Boncristiano, S, Bondolfi, L, et al.Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science. 2002;298(5597):1379.CrossRefGoogle Scholar
10.Relkin, N, Tsakanikas, DI, Adamiak, B, et al.A Double Blind, Placebo-Controlled, Phase II Clinical Trial of Intravenous Immunoglobulin (IVIG) for Treatment of Alzheimer’s Disease. Presented at: Annual Meeting of the American Academy of Neurology; April 12-19, 2008; Chicago, IL. Session S41.007Google Scholar

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 0
Total number of PDF views: 10 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 24th January 2021. This data will be updated every 24 hours.

Hostname: page-component-76cb886bbf-gtgjg Total loading time: 0.315 Render date: 2021-01-24T09:23:53.529Z Query parameters: { "hasAccess": "0", "openAccess": "0", "isLogged": "0", "lang": "en" } Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false }

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Current State of Immunotherapy for Alzheimer’s Disease
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Current State of Immunotherapy for Alzheimer’s Disease
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Current State of Immunotherapy for Alzheimer’s Disease
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *