My brain hurts

It’s a strange thing having your brain disappear.

Amy has encouraged me to write about it.

I’m not sure I can.

I was crying on the phone with my parents the other day, talking about how my grandfather started showing signs of Alzheimer’s at 56 (my age).

It’s emotionally complex and I’m not sure how to handle it.

But it’s happening.

I watched it in my grandfather, I know it’s happening to me.

And my 77-year old mother is going to be here in a couple of days after making a 30-hour flight half-way around the world to see her sick son.

BU researchers define possible molecular pathway for neurodegeneration in prion diseases

BU researchers define possible molecular pathway for neurodegeneration in prion diseases

https://www.eurekalert.org/pub_releases/2018-09/buso-brd092118.php

I wonder about prion diseases because I watched my grandfather degenerate from Alzheimers, and carried my suicidal grandmother into the Barrie, Ontario (that’s in Canada) hospital when I was 20 (that’s her, right, when I was a kid)

It sucked, and has scared me for 35 years.

But after years of therapy, I may be learning to deal with it.

My first book in 1997 was called Mad Cows and Mothers Milk for a reason.

A very personal reason.

A new study has shed light on the mechanisms underlying the progression of prion diseases and identified a potential target for treatment.

Prion diseases are a group of fatal neurological disorders that includes Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (“mad cow disease”). They are caused by the spread of “prions”, which are altered forms of normal cellular proteins. These abnormal molecules then interact with normal proteins to promote misfolding. While we understand that this process of converting normal to abnormal protein is what causes the symptoms of prion disease (including rapidly progressive dementia, seizures and personality changes), the exact mechanism of damage to the neuronal connections in the brain and spinal cord has been poorly understood.

Researchers from Boston University School of Medicine (BUSM) used a method they previously described for culturing nerve cells from the hippocampal region of the brain, and then exposing them to prions, to illustrate the damage to nerve cell connections usually seen in these diseases. They then added a number of different chemical compounds with known inhibitory effects on cellular responses to stressful stimuli, with the objective of identifying which pathways may be involved.

They found that inhibition of p38 MAPKα (an enzyme that typically responds to stress, such as ultraviolet radiation and heat shock) prevented injury to nerve connections and promoted recovery from the initial damage. Hippocampal nerve cells that had a mutation preventing normal function of p38 MAPKα were also protected, seeming to confirm the role the enzyme plays in this disease process.

David. A. Harris, MD, PhD, professor and chair of the Department of Biochemistry at Boston University School of Medicine and corresponding author of the study, sees these findings as a major breakthrough in trying to understand and treat these diseases. “Our results provide new insights into the pathogenesis of prion diseases, they uncover new drug targets for treating these diseases, and they allow us to compare prion diseases to other, more common neurodegenerative disorders like Alzheimer’s disease.”

These findings appear online in PLOS Pathogens.

 

Mental health

When I was a kid, we used to spend about every other weekend at my grandfather’s place in Cookstown, Ont., where my father grew up after being in Wales for 15 years.

I usually barfed on the way there, and the way back.

I was about 12-years-old, my sister was 10, and the grandparents decided to take us to Seaworld or whatever it was called in Niagara Falls.

That was when I first detected the Alheimers.

I didn’t know what it was then, just knew he was confused because instead of taking the Queen Elizabeth Way (QEW) exit in Toronto, he  took the Queensway Blvd. exit to some suburban area.

I said this is wrong, but he was set.

Eventually he found his way back to the proper highway and we went off to Niagara.

Seven years later, I was visiting him in a care facility and he had no idea who he was.

My grandma did the same thing, and eventually ended her life voluntarily.

I carried her into the emergency ward.

Mental health issues are common to many of us.

I only hope that sharing will provide optimism to others.

 

Going public(er): Alzheimer’s edition

Alzheimer’s has affected me, indirectly, in ways I still can’t understand, but am trying.

My grandfather died of Alzheimer’s in the 1980s, when I was a 20-something.

It wasn’t pretty, so stark that my grandmother took her own life rather than spend winter days going to a hospital where the man she had been with for all those years increasingly didn’t recognize her.

Glen Campbell’s death yesterday from Alzheimer’s, and Gene Wilder’s before that, rekindled lots of conflicting emotions.

In 1995, I was a cocky PhD student and about to be a father for the fourth time, when I was summoned to a meeting with, Ken Murray.

I rode my bike to a local golf club, met the former long-time president of Schneiders Meats, and established a lifelong friendship.

When Ken told me about a project he had established at the University of Waterloo in 1993, the Murray Alzheimer Research and Education Program (MAREP), after his wife’s demise from the disease, I said, I can’t understand the hell of being the primary caregiver for so long, but I know of the side-effects.

Ken had heard I might know something of science-and-society stuff, and he actually funded my faculty position at the University of Guelph for the first two years.

Sure, other weasels at Guelph tried to appropriate the money, but Ken would have none of it.

For over 20 years now, I’ve tried to promote Ken’s vision, of making the best technology available to enhance the safety of the food supply.

I’ve got lots of demons, and what I’ve learned is that it’s best to be public about them. It removes the stigma. It makes one recognize they are not alone. It’s humbling (and that is good).

In addition to being an unbelievably gifted songwriter, session player, and hit maker, Glen Campbell was – directly or not – an outstanding advocate of awareness about Alzheimer’s.

 

Michael Pollack writes in The New York Times obituary that Glen Campbell, the sweet-voiced, guitar-picking son of a sharecropper who became a recording, television and movie star in the 1960s and ’70s, waged a publicized battle with alcohol and drugs and gave his last performances while in the early stages of Alzheimer’s disease, died on Tuesday in Nashville. He was 81.

Tim Plumley, his publicist, said the cause was Alzheimer’s.

Mr. Campbell revealed that he had the disease in June 2011, saying it had been diagnosed six months earlier. He also announced that he was going ahead with a farewell tour later that year in support of his new album, “Ghost on the Canvas.” He and his wife, Kimberly Campbell, told People magazine that they wanted his fans to be aware of his condition if he appeared disoriented onstage.

What was envisioned as a five-week tour turned into 151 shows over 15 months. Mr. Campbell’s last performance was in Napa, Calif., on Nov. 30, 2012, and by the spring of 2014 he had moved into a long-term care and treatment center near Nashville.

Mr. Campbell released his final studio album, “Adiós,” in June. The album, which included guest appearances by Willie Nelson, Vince Gill and three of Mr. Campbell’s children, was recorded after his farewell tour.

That tour and the way he and his family dealt with the sometimes painful progress of his disease were chronicled in a 2014 documentary, “Glen Campbell: I’ll Be Me,” directed by the actor James Keach. Former President Bill Clinton, a fellow Arkansas native, appears in the film and praises Mr. Campbell for having the courage to become a public face of Alzheimer’s.

At the height of his career, Mr. Campbell was one of the biggest names in show business, his appeal based not just on his music but also on his easygoing manner and his apple-cheeked, all-American good looks. From 1969 to 1972 he had his own weekly television show, “The Glen Campbell Goodtime Hour.” He sold an estimated 45 million records and had numerous hits on both the pop and country charts. He was inducted into the Country Music Hall of Fame in 2005.

Decades after Mr. Campbell recorded his biggest hits — including “Wichita Lineman,” “By the Time I Get to Phoenix” and “Galveston” (all written by Jimmy Webb, his frequent collaborator for nearly 40 years) and “Southern Nights” (1977), written by Allen Toussaint, which went to No. 1 on pop as well as country charts — a resurgence of interest in older country stars brought him back onto radio stations.

Like Bobbie Gentry, with whom he recorded two Top 40 duets, and his friend Roger Miller, Mr. Campbell was a hybrid stylist, a crossover artist at home in both country and pop music.

Although he never learned to read music, Mr. Campbell was at ease not just on guitar but also on banjo, mandolin and bass. He wrote in his autobiography, “Rhinestone Cowboy” (1994) — the title was taken from one of his biggest hits — that in 1963 alone his playing and singing were heard on 586 recorded songs.

He could be a cut-up in recording sessions. “With his humor and energetic talents, he kept many a record date in stitches as well as fun to do,” the electric bassist Carol Kaye, who often played alongside Mr. Campbell, said in an interview in 2011. “Even on some of the most boring, he’d stand up and sing some off-color country song — we’d almost have a baby trying not to bust a gut laughing.”

After playing on many Beach Boys sessions, Mr. Campbell became a touring member of the band in late 1964, when its leader, Brian Wilson, decided to leave the road to concentrate on writing and recording. He remained a Beach Boy into the first few months of 1965.

Mr. Campbell had his most famous movie role in 1969, in the original version of “True Grit.” He had the non-singing part of a Texas Ranger who joins forces with John Wayne and Kim Darby to hunt down the killer of Ms. Darby’s father. (Matt Damon had the role in a 2010 remake.) The next year, Mr. Campbell and the New York Jets quarterback Joe Namath played ex-Marines in “Norwood,” based on a novel by Charles Portis, the author of “True Grit.”

Mr. Campbell made his Las Vegas debut in 1970 and, a year later, performed at the White House for President Richard M. Nixon and for Queen Elizabeth II in London.

But his life in those years had a dark side. “Frankly, it is very hard to remember things from the 1970s,” he wrote in his autobiography. Though his recording and touring career was booming, he began drinking heavily and later started using cocaine. He would annoy his friends by quoting from the Bible while high. “The public had no idea how I was living,” he recalled.

In 1980, after his third divorce, he said: “Perhaps I’ve found the secret for an unhappy private life. Every three years I go and marry a girl who doesn’t love me, and then she proceeds to take all my money.” That year, he had a short, tempestuous and very public affair with the singer Tanya Tucker, who was about half his age.

He credited his fourth wife, the former Kimberly Woollen, with keeping him alive and straightening him out — although he would continue to have occasional relapses for many years. He was arrested in November 2003 in Phoenix and charged with extreme drunken driving and leaving the scene of an accident. He pleaded guilty and served 10 nights in jail in 2004.

I cried with many emotions when I first watched his documentary, I’ll Be Me.

And I’ll watch it again today with humility, respect and gratitude, to people like Glen and Ken.

Going public: Alzheimer’s edition

My grandfather died of Alzheimer’s.

gene.wilderIt affected me in ways I still can’t understand.

It wasn’t pretty, so stark that my grandmother took her own life rather than spend winter days going to a hospital where the man she had loved for all those years increasingly didn’t recognize her.

So when Gene Wilder, who died of complications from Alzheimer’s at 83 on Monday, says, I didn’t want to tell anyone of my condition because I didn’t want to lose a fan’s smile, I don’t buy it.

I’ve got lots of demons, and what I’ve learned is that it’s best to be public about them. It removes the stigma. It makes one recognize they are not alone. It’s humbling (and that is good).

Gene Wilder was born Jerome Silberman in Milwaukee on June 11, 1933. His father, William, a manufacturer and salesman of novelty items, was an immigrant from Russia. His mother, the former Jeanne Baer, suffered from a rheumatic heart and a temperament that sometimes led her to punish him angrily and then smother him with

 “I don’t like show business, I realized,” he said in 2008. “I like show, but I don’t like the business.”

He was by then enjoying a new career as a novelist. His “My French Whore,” published in 2007, was the story of a naïve young American who impersonates a German spy in World War I (“just fluff, but sweet fluff,” the novelist Carolyn See wrote in her review in The Washington Post). It was followed by two more novels, “The Woman Who Wouldn’t” and “Something to Remember You By,” and a story collection, “What Is This Thing Called Love?”

Jordan Walker-Pearlman said  the cause was complications from Alzheimer’s Disease with which he co-existed for the last three years. The choice to keep this private was his choice, in talking with us and making a decision as a family.”

Could Alzheimer’s stem from infections like Salmonella

Gina Kolata of The New York Times reports on new research by a team of investigators at Harvard which suggests Alzheimer’s disease stems from the toxic remnants of the brain’s attempt to fight off infection.

salm.alzIt is still early days, but Alzheimer’s experts not associated with the work are captivated by the idea that infections, including ones that are too mild to elicit symptoms, may produce a fierce reaction that leaves debris in the brain, causing Alzheimer’s. The idea is surprising, but it makes sense, and the Harvard group’s data, published Wednesday in the journal Science Translational Medicine, supports it. If it holds up, the hypothesis has major implications for preventing and treating this degenerative brain disease.

The Harvard researchers report a scenario seemingly out of science fiction. A virus, fungus or bacterium gets into the brain, passing through a membrane — the blood-brain barrier — that becomes leaky as people age. The brain’s defense system rushes in to stop the invader by making a sticky cage out of proteins, called beta amyloid. The microbe, like a fly in a spider web, becomes trapped in the cage and dies. What is left behind is the cage — a plaque that is the hallmark of Alzheimer’s.

So far, the group has confirmed this hypothesis in neurons growing in petri dishes as well as in yeast, roundworms, fruit flies and mice. There is much more work to be done to determine if a similar sequence happens in humans, but plans — and funding — are in place to start those studies, involving a multicenter project that will examine human brains.

“It’s interesting and provocative,” said Dr. Michael W. Weiner, a radiology professor at the University of California, San Francisco, and a principal investigator of the Alzheimer’s Disease Neuroimaging Initiative, a large national effort to track the progression of the disease and look for biomarkers like blood proteins and brain imaging to signal the disease’s presence.

The work began when Robert D. Moir, of Harvard Medical School and Massachusetts General Hospital, had an idea about the function of amyloid proteins, normal brain proteins whose role had long been a mystery.

The proteins were traditionally thought to be garbage that accumulates in the brain with age. But Dr. Moir noticed that they looked a lot like proteins of the innate immune system, a primitive system that is the body’s first line of defense against infections.

Elsewhere in the body, such proteins trap microbes — viruses, fungi, yeast and bacteria. Then white blood cells come by and clear up the mess. Perhaps amyloid was part of this system, Dr. Moir thought.

glen-campbell-ill-be-me-movie-reviewHe began collaborating with Rudolph E. Tanzi, also at Harvard Medical School and Massachusetts General Hospital, in a study funded by the National Institutes of Health and the Cure Alzheimer’s Fund. The idea was to see if amyloid trapped microbes in living animals and if mice without amyloid proteins were quickly ravaged by infections that amyloid could have stopped.

The answers, they reported, were yes and yes.

In one study, the group injected Salmonella bacteria into the brains of young mice that did not have plaques.

“Overnight, the bacteria seeded plaques,” Dr. Tanzi said. “The hippocampus was full of plaques, and each plaque had a single bacterium at its center.”

In contrast, mice that did not make beta amyloid succumbed more quickly to the bacterial infection, and did not make plaques.