November 2018

Discovery of a New Antibody That Removes Amyloid Beta

In an article published in the Journal of Clinical Investigation, David Holtzman, a member of the Cure Alzheimer’s Fund Research Leadership Council, reported the discovery of a novel antibody against APOE called HAE-4 that reduced amyloid beta by half in a mouse model for Alzheimer’s disease. 

APOE plays a critical role in transporting cholesterol in the body. APOE variants are the largest single risk factor for Alzheimer’s disease. Because HAE-4 reduces amyloid beta levels without disrupting the levels of APOE in the blood, its discovery marks a critical moment in the field of Alzheimer’s research. According to Dr. Holtzman, “it turns out that APOE in the plaques has a different structure than the form of APOE found in the blood.” The fact that this novel antibody can recognize and clear APOE from the brain and not the blood makes it a powerful target for future clinical trials.

David M. Holtzman | M.D.


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The R(evolution) of Alzheimer’s in a Dish

In 2014, Drs. Rudy Tanzi and Doo Yeon Kim resolved one of the critical challenges of Alzheimer’s disease research: how to grow human brain cells that exhibit the hallmarks of Alzheimer’s pathology in a form mimicking that of a live brain, i.e. a gel. This new tool allowed for a more thorough testing of existing drugs, to determine whether they should be considered for clinical trials.

This year, Drs. Tanzi and Hansang Cho have expanded on the original Alzheimer’s in a Dish system to culture neural stem cells that, in addition to having elevated levels of amyloid beta and tau, also have the inflammatory factors known to contribute to neuroinflammation in Alzheimer’s disease.

Rudy Tanzi | Ph.D. & Hansang Cho | Ph.D.


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Targeting Protein Bundles Forming in the Brain at the Earliest Stages of Alzheimer’s

In a paper published in Molecular Neurodegeneration, Dr. Charles Glabe, a member of the Cure Alzheimer’s Fund Research Leadership Group, reports that treatment with a drug PLX3397 decreased the overall number of amyloid plaques in the brain and also altered the process of plaque formation. Importantly, treatment with this drug was most effective before the plaques developed. Mice that received PLX3397 performed better on a test for spatial and emotional memory but not spatial hippocampal memory. This paper discusses how a specific drug treatment could influence some specific aspects of hippocampal memory function but not others.


Charles Glabe | Ph.D.


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Why Certain Neurons Become Diseased—and Others Don’t

Major neurodegenerative diseases differ in the types of neurons and brain regions they destroy. Why some brain cells accumulate proteins while other, neighboring cells do not has remained a fundamental question in the field of Alzheimer’s research.

In a review published in Nature Neuroscience, Dr. Karen Duff, member of the Cure Alzheimer’s Fund Research Leadership Group, and her colleagues discuss the recent advances published in the area of selective neuronal vulnerability. The review explores the reasons why certain neurons become diseased while others only teeter on the brink of a catastrophic cliff. The group reports that the difference is due, in large part, to clearance mechanisms in the cells that keep misfolded or aggregated proteins in line. Neurons that are vulnerable to pathological proteins and are lost early in the disease include those present in the entorhinal cortex, the subiculum, the CA1 region of the hippocampus, and cholinergic neurons in the basal forebrain. Importantly, some cell types are vulnerable in the initial stage of the disease, while others are only affected later.


Karen Duff | Ph.D.


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The Role of Brain Vasculature in Neurodegenerative Disorders

A vast network of arteries, capillaries, and veins is required to keep the 86 billion neurons in the brain functioning properly. In a review published in Nature Reviews Neuroscience, Dr. Berislav Zlokovic, member of the Cure Alzheimer’s Fund Research Leadership Group, outlines the vascular dysfunction that precedes the pathology of Alzheimer’s disease and proposes a new model of Alzheimer’s disease biomarkers that links brain vascular changes to neurodegeneration.


Berislav Zlokovic | M.D., Ph.D.


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Using Genome Editing to Switch APOE4 to APOE3

Discussion of CRISPR-Cas9 genome editing has been making the rounds of 60 Minutes, Radiolab, and the pages of the New York Times. Dr. Li-Huei Tsai, member of the Cure Alzheimer’s Fund Research Leadership Group whose work on the subject has been published in Neuron, has used this powerful technique in order to provide new insights into the single greatest risk factor for sporadic Alzheimer’s disease, the APOE4 variant. Dr. Tsai and her colleagues have used CRISPR to convert APOE4 to the normal APOE3, alleviating Alzheimer’s-related phenotypes in neurons, glia, and organoids.


Li-Huei Tsai | Ph.D.


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Exercise and Improved Cognition

Imagine a future where the beneficial effects of exercise could be recreated in a brain ravaged by the cell loss, plaques, and tangles associated with Alzheimer’s disease. To this end, it would be crucial to first determine the biochemical changes that could improve memory in a brain experiencing the early stages of dementia. Drs. Rudy Tanzi, Se Hoon Choi, and their colleagues—whose research has just been published in Science—recently took a major step toward fulfilling this goal. The group uncovered how exercise and neurogenesis work collaboratively to enhance the likelihood that new neurons will survive to play a role in protecting against cognitive decline.

Rudy Tanzi | Ph.D. & Se Hoon Choi | Ph.D.


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NIH Director’s Pioneer Award—Dr. Jonathan Kipnis

Congratulations to Dr. Jonathan (Jony) Kipnis on being named a recipient of the NIH Director’s Pioneer Award. This prestigious award recognizes researchers who are pushing the boundaries of science by tackling research questions categorized as “high-risk; high-reward.” According to director of the NIH, Dr. Francis Collins, this award supports exceptionally innovative researchers who will have the potential to transform the biomedical field. This program is legendary for supporting cutting-edge and compelling biomedical research that may struggle in the traditional peer review process by nature of adopting an outside-the-box approach.

Dr. Kipnis’ research investigates the interactions between the immune system and the brain. His goal is to determine the mechanisms underlying the beneficial effects of the immune system in promoting brain function in neurodegeneration as well as in healthy aging. Dr. Kipnis recently had a breakthrough discovery, with a grant provided by Cure Alzheimer’s Fund, which was published in Nature and described lymphatic vessels that drain the central nervous system and serve as a connection between the brain and the immune system.


Dr. Jonathan Kipnis


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Interacting Glia in Alzheimer’s Disease

Glia cells make up between 33 – 66% of the total brain mass and include microglia, astrocytes, and oligodendrocytes. Microglia perform immune functions in the cell while astrocytes act as a scaffold for the nervous system.

In a newly published review in Frontiers in Neurology, Dr. Hansang Cho explores the new tools available to study the interactions between astrocytes and microglia during neurodegeneration. Brain inflammation involving glial cell activation is a prominent feature of Alzheimer’s disease. Dr. Cho points to studies suggesting that glial activation is thought to correlate with brain atrophy and cognitive impairments.


Hansang Cho | Ph.D.


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Eat More Fish!

The National Institutes of Health-AARP Diet and Health Study, which followed a total of 240,729 men and 180,580 women for 16 years, found that higher fish intake was significantly associated with lower total mortality. For women in the study, consumption of fish resulted in a lower Alzheimer’s disease mortality rate. The study was published by the Association for the Publication of the Journal of Internal Medicine and recommended by Nobel Laureate Dr. Paul Greengard, member of the Cure Alzheimer’s Fund Research Leadership Group.

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Evidence of the Link Between Alzheimer’s and Herpes Continues to Grow

In two independent studies, several prominent scientists funded by Cure Alzheimer’s Fund including Rudy Tanzi, Rob Moir, and Sam Gandy, along with their colleagues, have demonstrated that viruses, and herpes in particular, are involved in Alzheimer’s disease. The herpes virus can influence the activity of many human genes—including several that affect the risk of Alzheimer’s.

Rudy Tanzi | Ph.D. & Robert Moir | Ph.D.


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