How does Alzheimer disease damage and reduce the size of the brain?

Alzheimer disease damages the brain primarily through the progressive loss of neurons, which leads to a significant decrease in overall brain size and weight as the condition advances.1

This deterioration is associated with two primary tissue lesions found in the cerebral cortex:

• Neuritic plaques: These consist of deteriorating neuronal material surrounding deposits of a sticky protein called amyloid beta.21
• Neurofibrillary tangles: These are twisted fibers of the protein tau that form within nerve cells.21

While it is not fully understood whether these plaques and tangles are a cause or a consequence of the disease, they are believed to interfere with normal cellular functioning. Furthermore, the loss of neurons disrupts the synthesis of essential neurotransmitters—such as acetylcholine, norepinephrine, and serotonin—which are critical for interneuronal communication. As the disease progresses, this widespread neuronal death results in the characteristic shrinkage and atrophy of brain tissue.21