Antidepressant May Slow Progression of Alzheimer’s Disease

According to research by the Washington University School of Medicine, published in Science Translational Medicine, a common antidepressant can reduce the production of brain plaques.


Brain plaques correlate closely with memory problems and other cognitive impairments caused by Alzheimer’s disease. Stopping plaque buildup is believed to help halt the mental decline of Alzheimer’s patients. Scientists found the antidepressant citalopram stopped the growth of plaques in a mouse model of the disease. The research also found, in young adult humans who were cognitively healthy, that a single dose of the antidepressant lowered production of amyloid beta by thirty-seven percent. The researchers stress that while the results may be promising, any treatment at this point is premature.


Levels of amyloid beta, a protein produced by normal brain activity, rise in the brains of patients with Alzheimer’s, and eventually clump together to form plaques. Most antidepressants keep serotonin circulating in the brain, and this study was born from the theory that serotonin helps reduce plaque levels in cognitively health individuals.


For this research, scientists gave citalopram to older mice with brain plaques. They used two-photon imaging to track the growth of plaques in the mice for twenty-eight days. The results showed a rate of formation of new plaques decreased by seventy-eight percent. In a second experiment, the scientists gave citalopram to twenty-three people cognitively healthy people aged eighteen to fifty. Spinal fluid from the participants over the next day showed a thirty-seven percent drop in amyloid beta production.



  1. Sheline YI, West T, Yarasheski K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong C, Frederiksen C, Grzelak MV, Chott R, Bateman RJ, Morris JC, Mintun MA, Lee J-M, Cirrito JR. An antidepressant decreases CSF Ab production in healthy individuals and in transgenic AD mice. Science Translational Medicine, online May 14, 2014.
  2. Washington University in St. Louis. (2014, May 14). Antidepressant may slow Alzheimer’s disease. ScienceDaily. Retrieved May 16, 2014 from

By Emma Henson

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit


Amino Acids Improve Sleep in Mice with Traumatic Brain Injury

A study by Oregon Health and Science University, published in Science Translational Medicine, discovered a way to fix sleep disturbances in mice with traumatic brain injury. These results are important, because people commonly experience long-term and severe sleep and wakefulness issues after suffering concussions, a mild form of traumatic brain injury. The research hinged on feeding mice branched chain amino acids, something humans naturally produce from food. Dr. Miranda Lim, first author of the study, hopes that further studies will uphold the results found, and a dietary supplement prescribed as a viable therapy for concussions could be developed.


Nearly two million people in the US suffer traumatic brain injury every year, and nearly 72% have sleep disturbances. Sleep problems are not only frustrating, but physically harmful. The lack of rest impairs attention and memory formation for TBI patients, who already have a higher rate of functional disability and higher cost of rehabilitation. Treatments to remedy the dangerous swelling occurring after TBI exist, while underlying brain damage evident in sleep impairment as well as learning patterns remains without treatments.


The study compared mice with mild TBI to uninjured mice, and found the injured mice much less capable of staying awake for sustained periods of time. Scientists pinned this on underactive orexin neurons, meant to maintain wakefulness, mirroring spinal fluid evidence of human TBI patients. The scientists gave the injured mice a dietary therapy of branched chain amino acids; the building blocks of neurotransmitters, chemicals released by neurons in the brain. The results showed a restoration of normal orexin levels, and improved wakefulness. This offers a proof-of-principle for dietary intervention as a treatment for TBI, and hopefully an avenue to help brain-injured patients regain cognitive functions.



  • M. Lim, J. Elkind, G. Xiong, R. Galante, J. Zhu, L. Zhang, J. Lian, J. Rodin, N. N. Kuzma, A. I. Pack, A. S. Cohen. Dietary Therapy Mitigates Persistent Wake Deficits Caused by Mild Traumatic Brain Injury. Science Translational Medicine, 2013; 5 (215): 215ra173 DOI: 10.1126/scitranslmed.3007092
  • Oregon Health & Science University (2013, December 11). Dietary amino acids improve sleep problems in mice with traumatic brain injury. ScienceDaily. Retrieved January 7, 2014, from­ /releases/2013/12/131211185331.htm

By Emma Henson

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit

A cancer drug known as bexarotene was thought to have promise working against Alzheimer’s disease in mice, and began early clinical trials. However, a new study has put forward confusing results. Within a novel mouse model of AD, the disease appears to mimic the genetics and pathology of the human disease more completely than any other animal model. Bexarotene was found to reduce the levels of the protein amyloid-beta within experimental mice that had late-stage Alzheimer’s, and the protein levels were increased during the earlier stages. Researchers at the University of Illinois at Chicago College of Medicine presented the finding, and Mary Jo LaDu reported the results on July 16th during the Alzheimer’s Association International Conference in Copenhagen. Back in 2012, LaDu developed a transgenic mouse which currently carries a human gene that can increase the disease risk 15-fold, and is considered the most important genetic risk factor known for the disease.

Currently, Alzheimer’s disease is the most common form of dementia, and has hallmark signs of dense plaques in the brain that are composed of amyloid-beta proteins. However, new research has shown that smaller, more soluble forms of the protein are responsible for nerve cell death leading to cognitive decline, rather than solid plaques. Within humans, there is a gene that produces a protein within cells known as apolipoprotein E, and aids in clearing amyloid-beta protein from the brain by binding to it and breaking it down into smaller pieces. LaDu’s mice carry a gene variant known as APOE4, or APOE3. LaDu, professor of anatomy and cell biology at UIC, discussed that previous studies showed in comparison to APOE3, the apolipoprotein produced by the APOE4 gene did not bind as well to amyloid-beta, and did not clear the neurotoxin from the brain as it should have.

Previous studies that involved bexarotene’s effect in mice of AD have shown mixed results, and it was only the UIC research that was presented in Copenhagen to be the very first study to use mice that carried a human APOE gene, and to also develop similar AD pathology. LaDu worked alongside Leon Tai, a research assistant professor in anatomy and cell biology, and their coworkers to administer bexarotene to mice that carried either APOE4 or APOE3 for seven days during the early, intermediate, or late stages of the disease. The researchers then were able to measure the levels of soluble amyloid-beta within the brains of the mice. Results of the study showed that mice that carried human APOE4 that were in late-stage, there was a 40 percent reduction of soluble amyloid-beta, and an increase in the binding of the apolipoprotein to the amyloid-beta. However, in mice that carried either APOE3 or APOE4, and were earlier-stages, there was actually an increase in the amount of soluble amyloid-beta protein. When the APOE4 mice were given bexarotene for a month starting at early-stage AD, there was no beneficial effect in preventing the disease from progressing.

More research is needed to determine the proper length and timing of the bexarotene treatment, and whether it will benefit APOE3 carriers, and if APOE4 carriers will have beneficial short-term treatments. Bexarotene is also extremely toxic to the liver, and may not be useful during long-term studies, due to the toxicity concerns, and the dosing during AD studies would need to be completely controlled, and the patients closely monitored.



By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit

Anti-Tumoral Activity of a Short Decapeptide Fragment of the Alzheimer’s Abeta Peptide.

The inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Abeta peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell proliferation as determined by Ki67 immunostaining were observed following treatment with the Abeta fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Abeta derivative peptide may constitute a new antitumoral agent.

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Impaired orthotopic glioma growth and vascularization in transgenic mouse models of Alzheimer’s disease.

Alzheimer’s disease (AD) is the most common form of dementia among the aging population and is characterized pathologically by the progressive intracerebral accumulation of beta-amyloid (Abeta) peptides and neurofibrillary tangles. The level of proangiogenic growth factors and inflammatory mediators with proangiogenic activity is known to be elevated in AD brains which has led to the supposition that the cerebrovasculature of AD patients is in a proangiogenic state. However, angiogenesis depends on the balance between proangiogenic and antiangiogenic factors and the brains of AD patients also show an accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic. To determine whether angiogenesis is compromised in the brains of two transgenic mouse models of AD overproducing Abeta peptides (Tg APPsw and Tg PS1/APPsw mice), we assessed the growth and vascularization of orthotopically implanted murine gliomas since they require a high degree of angiogenesis to sustain their growth. Our data reveal that intracranial tumor growth and angiogenesis is significantly reduced in Tg APPsw and Tg PS1/APPsw mice compared with their wild-type littermates. In addition, we show that Abeta inhibits the angiogenesis stimulated by glioma cells when cocultured with human brain microvascular cells on a Matrigel layer. Altogether our data suggest that the brain of transgenic mouse models of AD does not constitute a favorable environment to support neoangiogenesis and may explain why vascular insults synergistically precipitate the cognitive presentation of AD.

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Characterization and use of human brain microvascular endothelial cells to examine β-amyloid exchange in the blood-brain barrier. Bachmeier C, Mullan M, Paris D.

Alzheimer’s disease (AD) is characterized by excessive cerebrovascular deposition of the β-amyloid peptide (Aβ). The investigation of Aβ transport across the blood-brain barrier (BBB) has been hindered by inherent limitations in the cellular systems currently used to model the BBB, such as insufficient barrier properties and poor reproducibility. In addition, many of the existing models are not of human or brain origin and are often arduous to establish and maintain. Thus, we characterized an in vitro model of the BBB employing human brain microvascular endothelial cells (HBMEC) and evaluated its utility to investigate Aβ exchange at the blood-brain interface. Our HBMEC model offers an ease of culture compared with primary isolated or coculture BBB models and is more representative of the human brain endothelium than many of the cell lines currently used to study the BBB. In our studies, the HBMEC model exhibited barrier properties comparable to existing BBB models as evidenced by the restricted permeability of a known paracellular marker. In addition, using a simple and rapid fluormetric assay, we showed that antagonism of key Aβ transport proteins significantly altered the bi-directional transcytosis of fluorescein-Aβ (1-42) across the HBMEC model. Moreover, the magnitude of these effects was consistent with reports in the literature using the same ligands in existing in vitro models of the BBB. These studies establish the HBMEC as a representative in vitro model of the BBB and offer a rapid fluorometric method of assessing Aβ exchange between the periphery and the brain.

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Depletion of CXCR2 inhibits γ-secretase activity and amyloid-β production in a murine model of Alzheimer’s disease.

Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to progressive cognitive decline. Recent studies from our group and others have suggested that certain G-protein coupled receptors (GPCRs) can influence the processing of the amyloid precursor protein (APP). Earlier, we demonstrated that stimulation of a chemokine receptor, CXCR2, results in enhanced γ-secretase activity and in increased amyloid-beta (Aβ) production. Taken together, results obtained from in vitro studies indicate that therapeutic targeting of CXCR2 might aid in lowering Aβ levels in the AD brain. To better understand the precise function and to predict the consequences of CXCR2 depletion in the AD brain, we have crossed CXCR2 knockout mice with mice expressing presenilin (PS1 M146L) and APPsw mutations (PSAPP). Our present study confirms that CXCR2 depletion results in reduction of Aβ with concurrent increases of γ-secretase substrates. At the mechanistic level, the effect of CXCR2 on γ-secretase was not found to occur via their direct interaction. Furthermore, we provide evidence that Aβ promotes endocytosis of CXCR2 via increasing levels of CXCR2 ligands. In conclusion, our current study confirms the regulatory role of CXCR2 in APP processing, and poses it as a potential target for developing novel therapeutics for intervention in AD.

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