ALZHEIMER DISEASE: PATHOLOGY
Alzheimer disease (AD) is the most common neurodegenerative disorder and affects 10% of people older than age 65 years and nearly 50% of those 85 years and older. The brain affected by AD has gross changes of brain atrophy accompanied by microscopic changes of amyloid plaques and neurofibrillary tangles.
The gross pathology of AD appears as enlargement of the ventricles and widening of the sylvian fissure secondary to cortical atrophy. Many convexal gyri are shrunken, and the sulci between these gyri are widened. The cerebral cortex may appear thin, and the basal ganglia are relatively small. The hippocampal region of the medial temporal lobe is affected early in the disease process and prominent atrophy of this region is usually observed. This region is responsible for storing new information, and its degeneration is associated with the prominent short-term memory impairment that is characteristic of AD.
Microscopic examination of the affected regions reveals plaques and neurofibrillary tangles, the pathologic hallmarks of AD. Plaques are primarily composed of extracellular accumulation of insoluble amyloid protein. The amyloid hypothesis speculates that the accumulation of amyloid is the critical trigger leading to the pathologic changes in the brain of AD patients and results in synapse loss, inflammation, neurofibrillary changes, and ultimately neuron death. Amyloid appears to accumulate years before the clinical symptoms and is associated with parallel worsening of brain atrophy. Neuroimaging techniques using positron emission tomography (PET) allow the presence and burden of amyloid deposits in the brain to be detected using radioligand labels. The molecular imaging of amyloid deposits has promise as a potential biomarker for AD and possibly may allow the identification of individuals who are still in the presymptomatic stages of the illness.
Neurofibrillary tangles are intracellular inclusions composed of aggregated tau proteins that normally function to stabilize axonal microtubules. Tau protein found in neurofibrillary tangles is in an abnormal state of hyperphosphorylation, which occurs in conjunction with its dissociation from microtubules and clumping as paired helical filaments. Neurofibrillary tangles are a ubiquitous accompaniment of aging, and accumulate with age in a predictable pattern. Individuals with AD tend to have more tangles, plaques, and neuron loss than individuals without dementia.