The causes of Alzheimer's disease are unknown, but the condition does have
theorized causes like acetylcholine deficiency and risk factors related to its
development. Alzheimer's disease is a progressive neurological (brain) disease
that leads to the loss of cognitive functions such as memory, thinking, and
reasoning.1
Complex brain changes can begin years or even decades before you experience
any symptoms. Researchers believe genetics combined with lifestyle and
environmental factors leads to the development of this condition.23 Here's
what you need to know.
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Theories
Alzheimer’s disease results in a significant loss of brain cells called neurons
and their connections, known as synapses. This loss starts in the areas of the
brain that control memory.
As damage spreads throughout the brain, more cognitive and physical abilities
are affected, causing the brain to shrink physically. There are two main
hypotheses for the development of Alzheimer’s: cholinergic and amyloid.4
Cholinergic Hypothesis
The cholinergic hypothesis is the earliest explanation of Alzheimer's disease.
Cholinergic neurons throughout the brain play an essential role in cognition,
including learning and understanding. People with Alzheimer's disease show a
severe loss of cholinergic neurons.5
Another theorized cause of Alzheimer's disease is a deficiency in the brain
messenger chemical called acetylcholine (ACh). ACh plays a role in brain
functions like learning and memory.5
Chen ZR, Huang JB, Yang SL, Hong FF. Role of cholinergic signaling in Alzheimer's disease.
Molecules. 2022;27(6):1816. doi:10.3390/molecules27061816
The only approved medications for Alzheimer's help maintain the level of ACh
in the brain. These drugs can temporarily slow down cognitive symptoms, but
they don't prevent long-term brain damage.5
Amyloid Hypothesis
For many years, researchers believed that abnormally high levels of
beta-amyloid—a protein that surrounds nerve cells—formed amyloid plaques
in the brain. These plaques are thought to contribute to the cognitive loss
associated with Alzheimer's disease. The beta-amyloid hypothesis was based
on an influential 2006 research paper.6
Treatment endeavors using medications to target beta-amyloid did not result
in improved symptoms of Alzheimer's disease. In addition, researchers found
that amyloid plaques can also be found in people without Alzheimer's disease
as they age.7
One report cast doubt on this hypothesis. One neuroscientist found that the
images in the 2006 study were altered. Since then, researchers have
approached the beta-amyloid hypothesis with caution.8
Results from the clinical trial of a medication called Leqembi (lecanemab)
showed some renewed support for the role of beta-amyloid in Alzheimer's
disease development. Lecanemab reduced the amount of amyloid in
participants' brains, resulting in a moderate improvement of symptoms after
18 months.9
More research and trials are necessary to confirm the debated hypothesis.
Investigators are also looking into new explanations for neuron loss as well.
Is Alzheimer’s Disease Hereditary?
Some cases of early-onset Alzheimer’s disease are familial, meaning children
may inherit certain mutations from their parents. In those cases, gene
mutations cause the disease. Consider speaking to a healthcare provider about
genetic testing if you have a history of early-onset Alzheimer’s disease in your
family.
About 70% of Alzheimer’s disease cases are related to genetic factors.10 The
genetics of late-onset Alzheimer’s disease is less clear: It doesn’t seem to run
in families.
The gene that can most affect your risk of late-onset Alzheimer’s is
apolipoprotein E (APOE). Everyone has some form (or variant) of APOE in
their DNA. You’re more likely to develop the disease if you inherit the ɛ4
variant. On the other hand, having the relatively rare APOE ε2 variant can
actually help protect you from Alzheimer’s disease.71112
