Diagnostic Features of Alzheimers


When analyzing the brain of a diagnosed Alzheimers Disease patient, two biological hallmarks are evident at the microscopic level: neurofibrillary tangles and senile plaques. Neurofibrillary tangles, or NFTs, disrupt the neurons resulting in the inhibition of nervous impulses. Basically, the neurons are unable to transmit messages, and the affected individual is unable to respond to environmental stimuli, therefore, losing control of the myriad functions characteristic of senile dementia. NFTs are made up of filament masses characterized by a paired helical structure within the neuronal cytoplasm1 . The paired helical structures are made up of abnormally phosphorylated tau protein. Tau protein regulates the dynamic instability of the microtubules in the cell, and is possibly associated with the polarity and bundling of microtubules. This phosphorylation causes the tau protein to associate with itself instead of binding with the microtubules, thus, resulting in paired helical structures. Although NFTs are best known as indicators of Alzheimers Disease, they are also found in the brains of persons afflicted with other neurological disorders, such as encephalopathic Parkinson's disease.

The arrows point to NFTs at low
magnification.
Image from http://www.uokhsc.edu/sections/neuropath/plaques.htm
The arrow points to a senile plaque at low magnification.
Image from http://www.uokhsc.edu/sections/neuropath/plaques.htm
Senile plaques are much larger and more complex structures than NFTs. A senile plaque is a complicated lesion consisting of degenerating nerves with a core consistent of beta amyloid protein2. Composed of 39-43 amino acids, this protein has an instinctive tendency to form insoluble aggregates3. Simply stated, the protein precipitates out of the cell fluid and solidifies causing an interruption of the normal tissue function. The abnormal neurites surrounding the central core originate from both axons and dendrites. Senile plaques seem swollen and are made up of the same material as NFTs4. There is a direct relationship between the number of senile plaques and both the severity of the clinical impairment and the decreased neurotransmission of acetylcholine. Because acetylcholine is associated with memory loss, it is believed that the senile plaques are a major cause of short term memory loss in Alzheimers disease1.


1 Edwardson et al.
2 "Untangling Alzheimers Disease." Internet. (1996). Netscape Online. (http://cait.cpmc.columbia.edu/news/frontiers/boif.html).
3 Kuroda, Y. et al. "Application of Long-Term Cultured Neurons in Aging and Neurological Research: Aluminum Neurotoxicity, Synaptic Degeneration and Alzheimers Disease." Gerontology. 41 (1994): 2-6.
4 Anderson et al.

Jennifer McGilton
mcgilton@u.arizona.edu
6 November 1997
http://student.biology.arizona.edu/ad