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According to experts,
as many as 50 million people worldwide may live with Alzheimer’s disease and similar
forms of dementia,
where harmful changes in the brain lead to a general decrease in cognitive functioning.
And memory loss is one of the first signs that something is wrong.
But earlier this week,
a team of researchers announced in the journal Brain
that they’ve developed a drug that successfully reverses Alzheimer’s-related memory loss.
Before you get too excited—the results were temporary.
And in mice.
So this isn’t a cure, and it has yet to be tested in humans,
but it’s still pretty exciting and is a big step towards an effective Alzheimer’s
treatment.
For most people with Alzheimer’s, symptoms start to appear in their mid-60s.
But the brain changes responsible for those symptoms typically start a decade earlier.
Those changes include clumps of proteins called amyloid plaques
and neurofibrillary tangles— the, tangling of thread-like proteins in neurons.
And as these plaques and tangles accumulate, neurons stop working and start to die.
Usually, some of the first areas of the brain to struggle are ones involved in memory.
A person with early-stage Alzheimer’s might have only minor problems remembering things,
but eventually, they may start repeating themselves,
getting lost in familiar places, and having trouble completing everyday tasks.
We don’t yet fully understand why the plaques and tangles form,
but scientists believe there’s a big genetic component.
And most recently, evidence has suggested it could be an epigenetic problem —
basically, something going wrong with the way genes are expressed.
The researchers in this study wanted to better understand the role of epigenetics in Alzheimer's
symptoms,
particularly memory loss.
One way cells control which genes are expressed is altering how DNA is packaged.
Each of your chromosomes is a long strand of DNA,
and if they were just loosely thrown in a cell’s nucleus without any organization,
well, it’d be like balling up a whole bunch of cords and just tossing them in a box.
Not only would your DNA get tangled, the cell would never be able to find anything it needed.
So your cells basically KonMari your genome
by carefully winding your DNA around proteins called histones.
And the tighter that winding is, the harder it is to access the DNA,
so genes in tightly-wound areas are expressed at lower levels.
Now, the cell can control what sections of DNA are packed away by removing or adding
molecules
to the DNA or the histones themselves.
For example,
enzymes called methyltransferases can add a methyl group to certain spots on a histone,
helping DNA bind more tightly and suppressing the expression of genes.
And the research team wondered if histone methylation could explain the memory problems
in Alzheimer’s patients.
For their study, they used a mouse model of the disease.
The mice have specific mutations which lead them to show signs of dementia as they age,
including developing plaques and memory problems.
The researchers also looked at human brain tissue from deceased Alzheimer’s patients,
specifically from their prefrontal cortices.
That’s the main area responsible for executive functions like working memory, planning, and
attention.
Sure enough,
in both the diseased human brain tissue and the brains of older mice,
they found increased methylation of a particular histone
and more of certain methyl-moving enzymes called EHMTs.
But the real question was whether this histone methylation actually causes memory problems.
So, the researchers took those Alzheimer’s mice and looked to see if inhibiting the enzyme
had any effect on their memories.
They trained those mice and normal control mice to perform a series of behavioral tests.
Then, all the mice had their brains injected for three days
with an engineered virus which was designed to reduce the amount of EHMTs in their cells.
Before the injections, the Alzheimer’s mice scored very poorly, sometimes doing no better
than chance on the memory tests.
But two weeks or so after the enzyme-stopping drug, they performed much more like normal
mice.
The injections seemed to restore their memory!
Two specific EHMT-inhibiting drugs also worked,
and continued testing of the mice suggested the restorative effects could last
as long as four days.
To really demonstrate the histone connection, though,
the researchers looked at the brains of the Alzheimer’s mice after the treatment—
and sure enough, there were fewer methylated histones.
When they dug deeper,
they found that the genes to make glutamate receptors
were among those whose expression had been reduced before the treatment.
Now, glutamate is a neurotransmitter essential for communication between neurons.
So, stopping that methyl-adding enzyme seems to let the neurons talk to each other better,
which the researchers think is a big part of how the treatments reverse the disease-related
memory loss.
Though, that might not be the only way they work.
They found that lots of genes throughout the genome were dampened
by the methylated histones.
And since Alzheimer’s disease is a complex disorder that isn’t caused by any one gene,
the researchers say a multifunctional treatment like this could battle the disease on several
fronts.
This isn’t the first time people have proposed treating Alzheimer’s by reducing histone
methylation,
but now, researchers have demonstrated it could actually work.
And while these findings are exciting, it’s important to mention what the injections /didn’t/
do.
At best, they were a short-term fix.
While they treated some of the symptoms of Alzheimer’s, the effects wore off,
so it didn’t cure the root cause of the disease.
And, it’s worth saying this again: this memory restoration has only happened in mice.
While human brains with Alzheimer’s disease show similarly elevated levels of the enzymes
in question,
it will take a lot more work to determine if the drugs are safe to use in people,
let alone whether they work.
So it’ll be awhile before this research leads to any clinically-relevant changes
in the way doctors approach Alzheimer’s.
Still, it’s pretty great that this worked at all.
The research has put scientists several steps closer to figuring out what Alzheimer’s
actually does to brains.
And that means they’re that much closer to finding an effective treatment.
Thanks for watching this episode of SciShow News!
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research that changes what we thought we knew about the world, or the science behind the
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