Alzheimer vaccine: amyloid‐β on trial

Robinson, Stephen R.; Bishop, Glenda M.; Münch, Gerald

doi:10.1002/bies.10236

Cited by 26 publications

(20 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Due to the concerns about the inflammatory effects of antibody injection (Robinson et al 2003), other compounds that have Ab binding capacity without immunomodulative effects have been explored in mice. Both gelsolin (Chauhan et al 1999) and ganglioside G M1 (Choo-Smith et al 1997) bind Ab with high affinity, and gelsolin also co-immunoprecipitates with Ab in human plasma (Chauhan et al 1999).…”

Section: Mousementioning

confidence: 99%

Maximizing the Potential of Plasma Amyloid-Beta as a Diagnostic Biomarker for Alzheimer’s Disease

Troncoso

Tucker

2008

Neuromol Med

View full text Add to dashboard Cite

Amyloid plaques are composed primarily of amyloid-beta (Abeta) peptides derived from proteolytic cleavage of amyloid precursor protein (APP) and are considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis. Presently, AD is diagnosed after the onset of clinical manifestations. With the arrival of novel therapeutic agents for treatment of AD, there is an urgent need for biomarkers to detect early stages of AD. Measurement of plasma Abeta has been suggested as an inexpensive and non-invasive tool to diagnose AD and to monitor Abeta modifying therapies. However, the majority of cross-sectional studies on plasma Abeta levels in humans have not shown differences between individuals with AD compared to controls. Similarly, cross-sectional studies of mouse plasma Abeta have yielded inconsistent trends in different mouse models. However, longitudinal studies appear to be more promising in humans. Recently, efforts to modify plasma Abeta levels using modulators have shown some promise. In this review, we will summarize the present data on plasma Abeta in humans and mouse models of AD. We will discuss the potential of modulators of Abeta levels in plasma, including antibodies and insulin, and the challenges associated with measuring plasma Abeta. Modulators of plasma Abeta may provide an important tool to optimize plasma Abeta levels and may improve the diagnostic potential of this approach.

show abstract

Section: Mousementioning

confidence: 99%

Maximizing the Potential of Plasma Amyloid-Beta as a Diagnostic Biomarker for Alzheimer’s Disease

Troncoso

Tucker

2008

Neuromol Med

View full text Add to dashboard Cite

show abstract

“…A␤ is produced by normal cells and usually exists as a soluble monomeric molecule and has diverse functions in the brain (177). A␤ is amphipathic and, although it has a high tendency to self-associate, to oligomerize, and to form fibrils, under normal conditions A␤ prefers to associate with lipoproteins (178).…”

Section: In Dementiamentioning

confidence: 99%

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

Lane

Farlow

2005

Journal of Lipid Research

157

128

View full text Add to dashboard Cite

“…These promising observations led to a clinical trial with active immunization using synthetic Ab . However, the trial was discontinued due to the occurrence of meningoencephalitis in 6% of cases without a clear correlation to the strength of the anti-Ab Ab response in these patients (3)(4)(5). Furthermore, immunotherapeutic approaches in animal models of AD provided controversial results with respect to cognitive improvements.…”

mentioning

confidence: 99%

Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System

Vollmar

Kullmann

Thilo

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Active immunization with amyloid-β (Aβ) peptide 1–42 reverses amyloid plaque deposition in the CNS of patients with Alzheimer’s disease and in amyloid precursor protein transgenic mice. However, this treatment may also cause severe, life-threatening meningoencephalitis. Physiological responses to immunization with Aβ1–42 are poorly understood. In this study, we characterized cognitive and immunological consequences of Aβ1–42/CFA immunization in C57BL/6 mice. In contrast to mice immunized with myelin oligodendrocyte glycoprotein (MOG)35–55/CFA or CFA alone, Aβ1–42/CFA immunization resulted in impaired exploratory activity, habituation learning, and spatial-learning abilities in the open field. As morphological substrate of this neurocognitive phenotype, we identified a disseminated, nonfocal immune cell infiltrate in the CNS of Aβ1–42/CFA-immunized animals. In contrast to MOG35–55/CFA and PBS/CFA controls, the majority of infiltrating cells in Aβ1–42/CFA-immunized mice were CD11b+CD14+ and CD45high, indicating their blood-borne monocyte/macrophage origin. Immunization with Aβ1–42/CFA was significantly more potent than immunization with MOG35–55/CFA or CFA alone in activating macrophages in the secondary lymphoid compartment and peripheral tissues. Studies with TLR2/4-deficient mice revealed that the TLR2/4 pathway mediated the Aβ1–42-dependent proinflammatory cytokine release from cells of the innate immune system. In line with this, TLR2/4 knockout mice were protected from cognitive impairment upon immunization with Aβ1–42/CFA. Thus, this study identifies adjuvant effects of Aβ1–42, which result in a clinically relevant neurocognitive phenotype highlighting potential risks of Aβ immunotherapy.

show abstract

Alzheimer vaccine: amyloid‐β on trial

Cited by 26 publications

References 58 publications

Maximizing the Potential of Plasma Amyloid-Beta as a Diagnostic Biomarker for Alzheimer’s Disease

Maximizing the Potential of Plasma Amyloid-Beta as a Diagnostic Biomarker for Alzheimer’s Disease

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System

Contact Info

Product

Resources

About