Hypotheses
Amyloid-beta and tau protein

In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.
The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade.[46] In this model, hyperphosphorylated tau begins to pair with other threads of tau as paired helical filaments. Eventually, they form neurofibrillary tangles inside nerve cell bodies.[65] When this occurs, the microtubules disintegrate, destroying the structure of the cell's cytoskeleton which collapses the neuron's transport system.[66]

A number of studies connect the misfolded amyloid beta and tau proteins associated with the pathology of Alzheimer's disease, as bringing about oxidative stress that leads to chronic inflammation.[67] Sustained inflammation (neuroinflammation) is also a feature of other neurodegenerative diseases including Parkinson's disease, and ALS.[68] Spirochete infections have also been linked to dementia.[9] DNA damages accumulate in AD brains; reactive oxygen species may be the major source of this DNA damage.[69]