Head CT > Degenerative > Alzheimer's Disease > Pathophysiology

Alzheimer's Disease - Pathophysiology

One proposed etiology of Alzheimer’s disease speculates it results from the aberrant processing of amyloid precursor protein (APP). This glycoprotein is normally expressed in high concentrations on neuronal cell surfaces and is excreted in a soluble form into the extracellular space following cleavage by secretases. When one of these secretases, beta-secretase, is overly expressed, a non-soluble amyloidogenic peptide fragment is generated. It is surmised that this fragment when accumulated extracellularly initiates an inflammatory cascade resulting in oxidative damage and eventual cell death.

Large cortical neurons in the transentorhinal region are the major types of neurons that undergo this degeneration. This process begins focally in the fronto/temporal lobes (primarily the entorhinal cortex and hippocampal regions) succeeded by the parietal lobes and finally the occipital lobes. The neuronal loss is severe resulting in marked, diffuse atrophy that may be as much as 10-30% of the total brain mass.

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