How About Some Good News?

Researchers have found a compound in the brain, which once depleted, makes the plaques of Alzheimer's disappear in mice.

I was grandma's girl. No doubt about it. She made clothes for me, including a pair of purple corduroy knickers I just loved. I spent weeks during the summer with her going to the club she and my grandfather belonged to, making a general nuisance of myself with the grandchildren of her friends. I knew the corners of her home and the creaks in the floorboards as well as I knew them in my own home. Being a child that moved around with my family, in some ways my grandmother's house was "home" in the enduring sense of the word. It was on the same street my dad grew up on, kept the bizarre wallpaper in the hallway and I always had the same room to sleep in.

My grandmother was also sharp as a tack with a sharp tongue. While it was rarely used on me, she had high expectations and made no bones about it. She had been a registered nurse, though retired in my memory. She was also a heavy consumer of the news. I remember the Sunday shows in particular, especially Meet the Press, because there was no negotiating out of them to watch cartoons.

Sometime in my mid-teens, my grandmother started to exhibit personality changes. The sharp tongue usually reserved for adults and whatever politician she was yelling at on Sunday morning became the norm. As the changes progressed she would lose words, forget things that just happened and let things like her weekly hair appointment slide. Eventually when I was 17, she was diagnosed with Alzheimer's.

Unless you have been through the progression of this type of disease with a loved one, you can't understand the pain and devastation that accompanies watching someone lose the very core of who they are. As time passes, the very touchstones of their personality fade, their memories vanish and at some point they look at you and don't know who you are. That happened the day of my oldest daughter's christening. She could not determine my place in her life or my name, but was completely enamored with the baby. Two years later, at my brother's wedding, she greeted me cordially as she would an acquaintance.

For every family that has been touched by this disease, it feels like a game of Russian Roulette. I watched my father like a hawk for the symptoms my grandmother exhibited and as I get older wonder if I'm next every time I can't find a word or have trouble recalling a name. It doesn't help that I look in the mirror every morning and see a younger version of my grandmother's face staring back.

There is good news afoot for families like mine. One of the diagnostic features of Alzheimer's is the formation of large amyloid plaques in the brain that disrupt the function of neuronal synapses. These are caused by an abnormal buildup of beta-amyloid peptide. Researchers at the Cleveland Clinic Lerner Research Institute have completed a study that demonstrated a gradual depletion of BACE1, a precursor to beta-amyloid peptide, actually makes the plaques disappear in mice with Alzheimer's. It also reversed other physiological hallmarks of the disease and improved memory and learning.

According to researcher Rinquan Yan :

To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer's disease mouse models.

Further examination of brain activity showed that synaptic function, the way information is transferred between neurons, was not fully restored in the mice treated by gradual depletion of BACE1. This may indicate that some amount of the substance is required for optimal cognition. But the results are still a giant step forward and the implications for future treatment are very positive and provide direction to other researchers:

Our study provides genetic evidence that preformed amyloid deposition (plaques) can be completely reversed after sequential and increased deletion of BACE1 in the adult," says Yan. "Our data show that BACE1 inhibitors have the potential to treat Alzheimer's disease patients without unwanted toxicity. Future studies should develop strategies to minimize the synaptic impairments arising from significant inhibition of BACE1 to achieve maximal and optimal benefits for Alzheimer's patients.

I was 33 when my grandmother passed away. It had been over 10 years since she had said my name or recognized my face. She had four great-grandchildren she never had the chance to know and several of her grandchildren never knew her before the Alzheimer's took the most interesting and remarkable parts of her personality away. I thought I had said goodbye to the woman I knew years before and would be relieved she had gone home. I was shocked at the amount of anger I felt for so many years of cognitive decline in a woman I once viewed as invincible.

May this research move quickly from breakthrough to therapy, for the sake of patients in the early stages of the disease and those who may be impacted in the future.

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Having gone through an all to familiar story, I try not to get my hopes to high. One can only pray this is finally the breakthrough.