“Common thread, silver bullet, naïve hope?” (Dr. Golbe’s musings)

Dr. Larry Golbe, a world-renowned expert on progressive supranuclear palsy (PSP), has his own blog (psp-blog.org) to which he occasionally publishes insights into the latest research.

In late March 2022, he published about two papers he read on the protein TMEM106B.  He says, “This stuff is known to be a component of healthy lysosomes and endosomes, components of the cell’s garbage disposal mechanism.”

[One paper] found that the brains of healthy elderly persons have abnormal aggregates of a misfolded form of the protein TMEM106B.  These abnormal aggregates were found “even more abundantly in a raft of neurodegenerative diseases: Alzheimer’s, CBD, multiple types of FTD, Parkinson’s, dementia with Lewy bodies, multiple system atrophy and multiple sclerosis.

The second paper (authors from Columbia University, Mayo Clinic Jacksonville, etc) “found the same TMEM106B aggregates” in those with PSP. 

Dr. Golbe says,  

An interesting finding is that unlike tau, TMEM106B misfolds the same way in all the diseases analyzed so far.  This may have huge potential implications: if (and this is a big “if”) the misfolded TMEM106B plays an important role in the formation of the misfolding and toxicity of tau and the other disease-specific proteins, and if (another big “if”) this misfolding is the rate-limiting step in the loss of brain cells in the neurodegenerative disorders, THEN preventing TMEM106B from forming or from misfolding, or targeting it with antibodies or drugs could be the silver bullet that prevents all of these diseases, PSP included.  That could be a naïve hope…

Read Dr. Golbe’s blog post here

“Common thread, silver bullet, naïve hope?”
Dr. Larry Golbe
March 16, 2022

Let’s hope!

Big News: PET Scan Detects Alpha-synuclein in Those with MSA (Alzforum)

Here’s an excerpt from an Alzforum article on this big research news:


For the first time, scientists have detected α-synuclein aggregates lurking in the brains of the living. This thanks to 18F-ACI-12589, a new tracer developed by AC Immune in Lausanne, Switzerland. Presented at AD/PD 2022…the first PET scans using the tracer showed uptake in the cerebellar white matter of people with multiple system atrophy (MSA). … Alas, PET signals were undetectable in the brains of people with other synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, despite selective binding of the tracer to postmortem brain samples of people who had died with those disorders.

This tracer was studied in both types of MSA — MSA-cerebellar (MSA-c) and MSA-parkinsonian (MSA-p).  Even in the MSA-p subtype, the cerebellum is affected by alpha-synuclein pathology.  The Alzforum article notes:  

Though people with either MSA subtype evinced binding in these regions, it was greater, on average, in those with MSA-c. Tracer uptake in cerebellar white matter completely distinguished people with MSA from controls and from those with other synucleinopathies, none of whom had significant uptake in this region.

These disorders are all synucleinopathies — multiple system atrophy (MSA), Parkinson’s disease (PD), Lewy body dementia (LBD), and dementia with Lewy bodies (DLB).  It is interesting that this new PET tracer only showed uptake in MSA.  The Alzforum article asks this question:   

Why the tracer fell short in people with other synucleinopathies remains unclear. [Reearchers] suspect it is because they have far fewer deposits, and tracer binding may have been too weak to detect them. Differences in α-synuclein fibril conformation, or in where the aggregates are in the brain, could also contribute.

The Alzforum article explained the decades-long difficulties in developing an alpha-synuclein tracer:  

The road to synuclein imaging has been long and strewn with obstacles. Compared to amyloid plaques and neurofibrillary tangles, α-synuclein fibrils exist in low concentrations in the human brain. This, combined with its intracellular location and myriad structural conformations, makes α-synuclein a tough target for PET tracers.

See the full article on Alzforum.
In First for the Field, α-Synuclein PET. Only for Multiple System Atrophy
26 Mar 2022

This is exciting news!

“Chronic Disease, Your Healthy Spouse, and Sex” (article)

Many chronic conditions (and medications used to treat these conditions) can affect sexual interest.  This is true for all of the atypical parkinsonism disorders and Parkinson’s disease.

Health Central has a good article on this topic.  Excerpt: 

Marriage is hard for everyone, but it can be even harder when one person has a chronic condition. Disease, illness, and disability can make a partner seem like a different person. That’s no one’s fault, says Laurel Wittman, board president of the Well Spouse Association…  “This is an area that people really struggle with,” she says. While some partners come together to find ways to sustain physical intimacy, for others the situation takes a huge toll on the relationship.

Read the full article here:

Chronic Disease, Your Healthy Spouse, and Sex
Health Central
March 21, 2022

“Genetic Testing May Influence Treatment of Neurologic Disorders”

Excerpts from this recent article in Brain & Life (brainandlife.org) magazine:

“Identifying genetic mutations associated with neurologic disorders may influence treatment and management—and inform decisions about getting tested. … Researchers are still working to understand exactly how these variants interact with each other and with the environment to cause disease. Many of the more common neurologic conditions such as multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease are associated with less severe variants in multiple risk genes, but in some cases they are produced by variants in single causative genes. … If people have puzzling neurologic signs or symptoms, or if one or more neurologic conditions seem to run in their families, should they pursue genetic testing?  The answer depends on the disorder and the usefulness of the information to people and their doctors, according to experts.”

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“Their Dementia Diagnosis Doesn’t Mean They’re Keeping Silent” (WSJ)

This terrific article from the Wall Street Journal in the fall of 2021 notes: 

“As the number of people with dementia grows, more of them are speaking out to challenge assumptions about what they can and can’t do.  A group of advocates, many in the earlier stages of this condition, say that people around them often struggle with understanding the full range of symptoms. …  Life expectancy for those with early-onset dementia varies. One 2019 study showed a mean survival time of 17 years after symptoms start and 10 years after a diagnosis.” 

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