Why is Alzheimer’s disease so difficult to treat? - Krishna Sudhir
Around the world, tens of millions
of people have Alzheimer's disease,
a debilitating brain disorder that
gradually destroys a person's memory
and other cognitive abilities.
It takes a heavy toll on both
patients and families,
as caring for a loved one with Alzheimer's
can be emotionally overwhelming
and financially difficult.
While doctors have studied
Alzheimer's for decades,
conducting hundreds of clinical trials,
there is still no effective preventive
treatment or cure.
So, why is Alzheimer's disease
so difficult to treat?
Alzheimer's accounts for 60 to 80%
of all dementia patients worldwide.
Dementia is a broader term,
used to describe a variety of conditions
that affect a patient's memory,
thinking skills, and everyday functions.
Most Alzheimer's patients first notice
symptoms in their 60s,
experiencing mild memory problems,
like losing track of dates
or forgetting what they just learned.
Some experience other changes,
like frequent shifts in mood,
increased anxiety and agitation,
and problems with coping
in new situations.
Symptoms typically progress
gradually over years
and eventually a person with Alzheimer's
may require constant care.
Some rare forms of Alzheimer's are caused
by a single inherited gene variant.
But most of the time Alzheimer's
is due to the complex interaction
of multiple genes in combination with
lifestyle and environmental factors,
so it's impossible to predict
who will develop the disease.
Alzheimer's involves a long,
chronic process,
resulting in many changes to the brain,
that likely starts to unfold at least 1 to
2 decades before symptoms first appear.
So it's been difficult
for scientists to pinpoint
exactly what triggers this process
and what causes the many symptoms
of Alzheimer's.
But thanks to continued research, they're
beginning to put this puzzle together.
Initially, scientists noticed that
the brains of Alzheimer's patients
display an abnormal buildup of
a compound called beta-amyloid.
Beta-amyloid is created
when a large protein,
amyloid-beta precursor protein, or APP,
is broken down.
APP plays an essential role in the brain,
aiding in neural growth and repair.
However, in Alzheimer's patients, it's
thought that APP is improperly cleaved,
creating sticky beta-amyloid byproducts,
which easily clump together.
These plaques can build up in the spaces
between neurons,
and interfere with normal brain signaling.
But this likely isn't the full story.
While all patients with Alzheimer's
have plaques,
not all people with plaques have
or will develop dementia.
And Alzheimer's symptoms don't
always become more severe
as plaques accumulate in the brain.
In the 1980s, another protein, tau,
emerged as a possible contributor.
Tau's normal role is as
a scaffolding protein,
to help reinforce the internal structure
of neurons and give them their shape.
But in Alzheimer's patients,
tau is modified and misfolded,
causing it, like beta-amyloid,
to become sticky and to clump.
These tau tangles accumulate
within neurons and are toxic,
causing the cells to eventually die.
In patients, plaques normally
appear before tangles,
yet questions still remain.
Do amyloid plaques trigger
tau dysfunction?
And why exactly do these abnormal proteins
lead to such specific disease symptoms?
To make matters more complex,
recent studies have found that Alzheimer's
is closely linked to changes
in the way immune cells, called microglia,
function in the brain.
Others have found that Alzheimer's
may also be caused by problems
in the junctions between neurons,
called synapses.
And alterations in the way the brain
produces and burns energy
may also be an underlying factor.
Together, all this suggests that
Alzheimer's is likely caused
by a complex cascade of events.
And teasing out the order of events,
and how to stop it once it starts,
will take more research.
But there are things patients can
do to better manage symptoms.
Staying active, learning new skills,
and even participating
in daily activities,
like household chores,
seems to slow disease progression.
Medications that target neurotransmitters,
the brain's signaling molecules,
can slow memory loss
and help with learning and reasoning.
And scientists continue to develop
new therapies.
For example, drugs that target
beta-amyloid have shown promise
in slowing the disease and reducing plaque
accumulation in the brain.
Alzheimer's disease won't
go away anytime soon.
Dementia cases are expected
to double in the next 20 years.
But continued research holds
the promise of better treatment
and perhaps one day, prevention,
as scientists piece the Alzheimer's
puzzle together.
