Clinical Research & Treatment
Alzheimer’s Disease
Cholinesterase-inhibitors (ChEIs) are a group of medicines that block the normal breakdown of
acetylcholine. Acetylcholine is the main neurotransmitter found in the body and has functions in
both the peripheral nervous system and the central nervous system.
• Reduce synaptic breakdown of the neurotransmitter acetylcholine
• Targets the intrinsic cholinergic system in the brain
• Improvements in attention, memory.
Amyloid cascade hypothesis
The amyloid cascade hypothesis posits that the deposition of the amyloid-β peptide in the brain
parenchyma is a crucial step that ultimately leads to Alzheimer's disease.
The amyloid accumulation starts very early and is asymptomatic. It’s the hyper-phosphorylation of
tau that causes the neurodegeneration and leads to symptoms. Not the amyloid on its own but in
combination with tau toxicity.
Recent research and treatment
Treatment aimed at amyloid toxicity
• Goal: removing / reducing amyloid
• To reduce synaptic toxicity
• What has been studied?
o Immune therapy (vaccination /antibodies against amyloid-beta)
o Targeting enzymes (BACE, gamma-secretase) that ‘produce’ amyloid-beta
Pitfalls of anti-amyloid treatment
• Too little, too late:
• Little: Synaptic toxicity: not only amyloid, but also tau, inflammation, …
• Late; Widespread synaptic breakdown is irreversible
• Other pathology (tau, inflammation) may continue, even if amyloid is removed
, Amyloid plaque reduction with aducanumab has been affective
but the cognitive effects of this treatment was really small.
Other treatment options
Reducing the risk factors for Alzheimer’s
is an important part of the options.
Alzheimer’s Disease
Cholinesterase-inhibitors (ChEIs) are a group of medicines that block the normal breakdown of
acetylcholine. Acetylcholine is the main neurotransmitter found in the body and has functions in
both the peripheral nervous system and the central nervous system.
• Reduce synaptic breakdown of the neurotransmitter acetylcholine
• Targets the intrinsic cholinergic system in the brain
• Improvements in attention, memory.
Amyloid cascade hypothesis
The amyloid cascade hypothesis posits that the deposition of the amyloid-β peptide in the brain
parenchyma is a crucial step that ultimately leads to Alzheimer's disease.
The amyloid accumulation starts very early and is asymptomatic. It’s the hyper-phosphorylation of
tau that causes the neurodegeneration and leads to symptoms. Not the amyloid on its own but in
combination with tau toxicity.
Recent research and treatment
Treatment aimed at amyloid toxicity
• Goal: removing / reducing amyloid
• To reduce synaptic toxicity
• What has been studied?
o Immune therapy (vaccination /antibodies against amyloid-beta)
o Targeting enzymes (BACE, gamma-secretase) that ‘produce’ amyloid-beta
Pitfalls of anti-amyloid treatment
• Too little, too late:
• Little: Synaptic toxicity: not only amyloid, but also tau, inflammation, …
• Late; Widespread synaptic breakdown is irreversible
• Other pathology (tau, inflammation) may continue, even if amyloid is removed
, Amyloid plaque reduction with aducanumab has been affective
but the cognitive effects of this treatment was really small.
Other treatment options
Reducing the risk factors for Alzheimer’s
is an important part of the options.
