• Compromised neuronal integrity & synaptic function

• Tau tangles

• CSF tau changes

• Amyloid plaques

• Reduced amyloid clearance

• Hippocampal volume changes

• Initial cognitive impairment begins

• Memory loss

• Metabolism changes

• Depression

• Behavioral changes

• Oxidative stress

• Inflammation

• Microglial activation

• Neuronal loss

• Death