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PMID: 19275636 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Immunotherapy, vascular pathology, and microhemorrhages in transgenic mice.

CNS & neurological disorders drug targets ·Vol. 8 ·No. 1 ·2009-03-00 ·Pages 50-64

Wilcock DM, Colton CA

Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that results in severe cognitive decline. Amyloid plaques are a principal pathology found in AD and are composed of aggregated amyloid-beta (Abeta) peptides. According to the amyloid hypothesis, Abeta peptides initiate the other pathologies characteristic for AD including cognitive deficits. Immunotherapy against Abeta is a potential therapeutic for the treatment of humans with AD. While anti-Abeta immunotherapy has been shown to reduce amyloid burden in both mouse models and in humans, immunotherapy also exacerbates vascular pathologies. Cerebral amyloid angiopathy (CAA), that is, the accumulation of amyloid in the cerebrovasculature, is increased with immunotherapy in humans with AD and in mouse models of amyloid deposition. CAA persists in the brains of clinical trial patients that show removal of parenchymal amyloid. Mouse model studies also show that immunotherapy results in multiple small bleeds in the brain, termed microhemorrhages. The neurovascular unit is a term used to describe the cerebrovasculature and its associated cells-astrocytes, neurons, pericytes and microglia. CAA affects brain perfusion and there is now evidence that the neurovascular unit is affected in AD when CAA is present. Understanding the type of damage to the neurovascular unit caused by CAA in AD and the underlying cause of microhemorrhage after immunotherapy is essential to the success of therapeutic vaccines as a treatment for AD.

MeSH Terms
Alzheimer Disease/complications,immunology,metabolism,therapy Amyloid beta-Peptides/immunology,metabolism Animals Antibodies/immunology,metabolism Cerebral Amyloid Angiopathy/complications,immunology Humans Immunotherapy/adverse effects,methods Intracranial Hemorrhages/etiology,immunology Mice Mice, Transgenic
Chemicals
Amyloid beta-Peptides Antibodies
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wilcock Donna M
Duke University Medical Center, Division of Neurology, Research Dr, Durham, NC 27710, USA. [email protected]
Colton Carol A
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Article Info
Journal
CNS & neurological disorders drug targets
Abbr.
CNS Neurol Disord Drug Targets
ISSN
1996-3181
DOI
10.2174/187152709787601858
Email
[email protected]
Published
2009-03-00
Pages
50-64
Language
English
Region
United Arab Emirates
NLM ID
101269155
PMCID
PMC2659468
Subset
IM
Grants
NIA NIH HHS · R01 AG019740 · United States
NIA NIH HHS · F32 AG030942 · United States
NIA NIH HHS · AG030942 · United States
NIA NIH HHS · AG19740 · United States
NIA NIH HHS · F32 AG030942-02 · United States
NIA NIH HHS · F32 AG030942-01 · United States
NIA NIH HHS · R01 AG019740-05 · United States
External Links
PubMed source DOI: 10.2174/187152709787601858 PMC Full Text View journal details
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