Immune response to Alzheimer disease-related protein changes as we age

August 01, 2003

Alzhemier disease (AD) is characterized by the progressive accumulation of amyloid b protein (Abeta) in areas of the brain serving cognitive functions such as memory and language. Active immunization with Abeta peptides has been shown to decrease Abeta-related lesions in the brain in mouse models of AD. Unfortunately, the first clinical trials for Abeta vaccination in humans were halted due to side-effects experienced by a small subset of subjects. However, these immunization strategies remain a viable concept in developing treatments for AD.

In the August 1 issue of the Journal of Clinical Investigation Howard Weiner and colleagues from Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts, have further characterized the immune response to Abeta in humans, and revealed intriguing reactions of the elderly human body to Abeta. The authors found that some healthy, elderly individuals, as well as those with AD, contained elevated levels of T cells reactive towards Abeta, when compared to healthy middle-aged adults. While the general trend is for a diminished immune response with age, this finding demonstrates a very selective increase in the Abeta-reactivity of T cells with age in both healthy and AD-affected individuals. The authors went on to characterize the particular regions of the Abeta protein and T cells that react. This reactivity has implications for the design of Abeta vaccines and may itself be linked to susceptibility and course of disease, and appears to be linked with the aging process.

In their accompanying commentary Drs. John Cirrito and David Holtzman from Washington University in St. Louis, Missouri discuss the implications of this study with regard to the development of Abeta vaccines.

TITLE: Increased T cell reactivity to amyloid b protein in older humans and patients with Alzheimer disease

Howard L. Weiner
Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Phone: 617-525-5300
Fax: 617-525-5252

View the PDF of this article at:

Amyloid-beta and Alzheimer disease therapeutics: The devil may be in the details

David M. Holtzman
Washington University School of Medicine, St. Louis, Missouri, USA.
Phone: 314-747-0286
Fax: 314-362-2826

View the PDF of this commentary at:

JCI Journals

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