Accelerated Cell Membrane Degradation in Alzheimer’s Disease Brain: Relationship to Amyloid Formation?

Abstract

Alzheimer’s disease is a degenerative brain disease first described by the German psychiatrist Alois Alzheimer (Alzheimer, 1907). His initial report was based upon the histological examination of brain tissue from a 51 year old female patient who experienced a rapid progressive deterioration of memory and died four and a half years after the onset of the first symptoms with total loss of mental functions. The brain of this woman showed generalized atrophy without macroscopic lesions. Using a novel silver staining method developed by Bielschowsky, Alzheimer found that more than a quarter of the cortical neurons contained fibrillary tangles, and that this abnormality was accompanied by the extracellular deposition of “multiple miliary lesions”, containing a “unique substance” which was later recognized to be amyloid. In his initial report, Alzheimer also described severe loss of nerve cells, which was most prominent in the upper layers of the brain cortex. More recently, Terry and colleagues used computerized image processing to confirm the loss of cortical neurons, and showed that large cortical neurons are particularly affected (Terry et al., 1981). Neuronal atrophy and the presence of degenerating neurites in the immediate vicinity of amyloid plaques has generated two controversial hypotheses: First, that amyloid is toxic to neurons, and, second, that amyloid is a byproduct of neuronal atrophy formed by neurons during their degeneration.