Stories of Hope: Alzheimer’s Disease (2014)

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Adele Miller knew what came next. She had lived it twice already: her father’s unraveling, due to Alzheimer’s disease, and, a few years later, her mother’s journey through the same erasure of mind and memory. So when doctors told her, at age 55, that she, too, had the disease, she remembered her parents’ difficult last years.

‘Tell no one,’ she told her family, “Keep it secret.”

“She was ashamed,” her daughter, actress, writer and director Lauren Miller, recalls. “She was so embarrassed because there’s such a stigma.” And she worried about her family. How would they handle all this? “I asked her once if she was scared,” Lauren says. “She said she wasn’t afraid for herself. But she was afraid for me, and my dad, and my brother. She knew what she’d gone through with her parents.”

Alzheimer’s disease has been a constant in the actress’s family. Perhaps that made her more attuned to the subtle changes that can herald the onset of the disease. At Lauren’s college graduation, she saw the first clues that something was amiss with her mother. She was repeating herself. Not just, “Oh, have I told you this before?” This was different. A few years later, as she and her mother prepared for a party, Lauren was stunned by the changes in her mother’s behavior. Her mother’s memory no longer seemed to function. She kept forgetting that the taco salad was vegetarian. She kept asking over and over where to throw the garbage. Lauren knew that’s not like her mother, a teacher for 35 years. So she sat down with her brother Dan and their dad. It was time to do something for Mom. “It’s not that my dad wasn’t noticing things. But I don’t think he wanted to admit there was a problem. And he was simply too close to it,” Lauren says.

It took less than five years for Alzheimer’s disease to rob Adele Miller of nearly everything. Before she turned 60, she couldn’t write. She couldn’t speak. She didn’t even recognize her family.

The loss, the sadness, and the anger that Alzheimer’s families feel is compounded by a sense of utter helplessness against a disease that yields to no drug. But Lauren decided she would not be helpless, and in 2011, she and her husband, actor Seth Rogen, launched Hilarity for Charity, which aims to raise Alzheimer’s awareness in young people while also raising funds for the Alzheimer’s Association. Now Hilarity for Charity also sponsors college fundraisers and hosts support groups for caregivers who are under 40.

“Seth has the ability to reach an audience that may not know much about Alzheimer’s. His fans are 16 year old boys who aren’t generally the target for Alzheimer’s awareness,” Lauren said. “But he was able to strike a cord with a lot of these young people. We get emails from people who are 16. ‘Thank you for doing this. I felt alone. Now there’s a voice.’ This is considered an old person’s disease, but it’s really not. It affects everyone.”

In December 2013, Lauren, co-writer, producer and star of the movie ‘For a Good Time, Call’ joined the CIRM governing Board, the Independent Citizens Oversight Committee, as a patient advocate for Alzheimer’s disease.

“Alzheimer’s research is woefully underfunded by the government, so it’s important to have bold, innovative approaches like CIRM’s to take research to the next level,” Lauren said. “Stem cell research is at the cusp of something life changing. To me, it’s one of the things closest to making a step toward treatment. I jumped at the opportunity to be part of it.”

For information about CIRM-funded Alzheimer’s disease research, visit our fact sheet.

CURING ALZHEIMER’S DISEASE

The mice were old. A t 18 months, they were near the end of their normal lifespan. Worse, the plaques and tangles that signal Alzheimer’s Disease ravaged their brains.

Unsurprisingly, their memories were worthless. They could be shown the safe harbor in a water maze — a test of mouse memory — every day and never remember where it was.

Frank LaFerla, Ph.D., director of the Institute for Brain Memory Impairments and Neurological Disorders at the University of California, Irvine, didn’t believe stem cells held promise for Alzheimer’s patients. But he let experiments decide the question.

LaFerla and his team injected neural stem cells into the hippocampus of the doddering mice. A month later, he put the mice into the water maze where they’d failed so miserably before. This time, the animals learned. They remembered. They performed every bit as well as their Alzheimer’s-free peers. But it was puzzling. When LaFerla looked at the brains of the stem-cell treated mice, the diagnostic markers for Alzheimer’s disease — amyloid plaques and neurofibrillary tangles — were still there.

“We found absolutely no difference,” LaFerla said. “This is unparalleled. This is the first time in our lab — or probably any lab — we’ve been able to improve Alzheimer’s without lowering plaque pathology. Likewise, we had no effect on tangle pathology.”

Adding to the puzzle, few of the new cells turned into neurons. But when LaFerla looked more closely, he found the brain’s learning center, the hippocampus, had new wiring — a dramatic increase in new connections between neurons, called synapses. The remaining neurons were branching and touching and talking to a greater number of other neurons than they had before the stem cells were injected.

“That was very interesting because the best correlate of cognitive decline is not plaques or tangles, but the degree of synaptic loss,” LaFerla said.

Further studies revealed that the stem cells kicked off this communications revolution by secreting something called brain-derived neurotrophic factor, or BDNF. The stem cells also induced all the surrounding brain cells to squirt more BDNF.

In fact, the researchers were able to inject BDNF into mouse brains and induce synaptogenesis, but at half the level induced by stem cells. This suggests that secreting BDNF is only part of what stem cells do, LaFerla said.

“We got into this not expecting it to work,” he said. “Now we know stem cells don’t need to replace neurons. By implanting stem cells into brains, there is almost a doubling of synaptic density.”