Over a century ago a German doctor called Alice Alzheimer spotted anomalies in brain sections from a patient with dementia.
Ever since people have been studying the strange plaques and tangles that he saw in the hope that we could one day understand and cure what is now known as Alzheimer’s disease.
Plaques are insoluble deposits of a peptide called amyloid beta or a beta.
They’re formed when a protein called amyloid precursor protein is sequentially cleaved by two enzymes beta and gamma-secretase.
Other molecules are generated by this cleavage and may play a role in the disease but a beta is the main culprit.
A beta tends to miss fold and become sticky eventually clumping together to form soluble oligomers.
Some of these aggregate into large in the soluble fibrillar the deposit in the brain as plaques.
The oligomers come in several forms or species.
We don’t know exactly which species are toxic but research shows that they linked in communication and plasticity at sign APS’s.
This could be what stops the brain and forming or retrieving memories.
Neurons aren’t the only cells affected in Alzheimer’s disease.
Astrocytes are microglia also play a role.
Microglia our immune cells that clear out waste and prune synapse is during development.
Microglia take up a beta but they also get activated by it triggering the release of inflammatory cytokines that can damage neurons.
The microglia also start to remove sign APS’s by phagocytosis.
As sign apses start to malfunction and neurons die abnormal patterns of activity emerge and eventually the brain can’t process and store information properly.
Another key feature of Alzheimer’s disease is neurodegeneration.
Neuronal death and damage is triggered by a beta but some of ABT’s effects seem to be mediated by another protein seen in the brains of patients tau a component of tangles.
In a healthy neuron, molecules are carried along the axon on a series of tracks made of microtubules and stabilized by the town.
but in Alzheimer’s disease tau is modified causing it to dissociate from the microtubules adopt an abnormal shape and move from the apps onto the cell body.
Like a beta, tau comes in a variety of forms and we don’t know which ones contribute to the disease.
and like a beta these forms either remain soluble or stick together and deposit as the tangles that dr. Alzheimer saw
Eventually, these processes kill the neuron.
Another problem seen in animal models is that Misfolded tau proteins can spread across synapses into healthy neurons.
There they make healthy tau proteins start to miss faults as well as spreading pathology across the brain.
The pattern of spreading through the different brain regions matches the changing symptoms from early to late stages of Alzheimer’s disease.
This pattern also reflects how certain neurons are more vulnerable than others to die.
Despite these advances in our understanding of Alzheimer’s disease no cure exists.
While drugs are being developed to target amyloid beta or tau it’s unclear whether they will eventually be successful in treating the disease.
There’s only one certainty continued support for basic and clinical research will enable us one day to diagnose and treat this devastating condition.