Your brain is able to store massive amounts of memories throughout your lifetime. There are cases, however, in which this ability progressively degrades and eventually disappears, giving way to problems with thinking, reasoning, and remembering. When these symptoms occurs faster than normal aging, it is termed dementia. Alzheimer’s disease (AD) is the most common form of brain function loss, and its neuropathology are summarized here.
In 1906 Dr. Alois Alzheimer noted symptoms of dementia in one of his patients, who experienced memory loss, unpredictable behavior, and depended on others to carry out all activities. After the patient passed away, he examined her brain tissue and noticed severe brain atrophy, an overall reduction in the size of the cerebral cortex and hippocampus (the center of learning and memory), and enlarged ventricles.
More than a century after Dr. Alzheimer published his observations, we can now visualize the changes that occur throughout the progression of the disease. Neurodegeneration starts 5 to 10 years before the onset of symptoms, so doctors rely on live imaging techniques to make early diagnoses of AD. Positron-emission tomography (PET) measures brain activity, with red indicating areas of the brain that are highly active, and blue indicating areas of low activity. Computed tomography (CT) scans help build a 3-dimensional representation of the brain. Brain atrophy, shown here by the enlarged ventricle cavities (black) and the widened white regions, can be observed in advanced stages of AD.
Dr. Alzheimer also noticed that many abnormal clumps and tangled bundles of fibers formed in the brain of patients with the disease. These amyloid-beta plaques and neurofibrillary tangles in medial-temporal lobe structures are two of the hallmark features of AD. Both these protein aggregates and the molecules that compose them have been shown to impair cognition.
The protein aggregation abnormalities present in AD patients (plaques and tangles) activate immune system cells (astrocytes and microglia) to degrade them. These cells release cytokines, which induce further damage in the brain. As a result, mitochondria cannot produce enough energy and oxygen consumption is impaired.
The damage induced by misfolded proteins, inflammation, and energy failure is believed to lead to massive synaptic and cell loss. The extent of damage is correlated with devastating effects on cognition. There are drastic changes taking place in the brains of AD patients, replacing an entire lifetime of memories, and researchers work tirelessly to understand them so that the symptoms of AD are ameliorated and resolved.