• AD is a progressive, degenerative disease that is characterized by confusion, loss of memory, disorientation, restlessness, speech disturbances, and hallucinations. (7)
• Initially Alois Alzheimer (a German neuropathologist) described AD in 1906.(7)
• AD is estimated to affect between 2.5 and 3 million people in the United States.(7)
• AD is the leading cause of dementia in the United States.(7)
• AD usually strikes after the age of 65 (7)
• In the early 1900's, only 4% of the United States population reached the age of 65. Today, 13% of the population is 65+. (10)
• The life expectancy in 1900 was 47, today it is over 76. (10)
• The average amount of time an individual actually lives with the symptoms of AD is 5 to 10 years. This time is being extended as the learning about the function and development of AD continues. (7)
• The only true diagnosis of AD is an autopsy.(7)

• Neurofibillary tangles are a major feature of AD.(13)
• NTs are constructed of massed corresponding spiral fiber that holds microtubule-associated tau protein.(13)
• The number of NTs in the parahippocampal cortex correlates with the number of IL-1alpha+ microglia and the number of S100B+ astrocytes in the same area.(13)
• It appears that the more tangles there are in the cognitive sections of the brain, the greater the level of dementia.(13)
• There are variations in the structures of the tangles which are thought to change (or progress) over the process of AD. (13)
• There are 4 different types of neurofibrillary tangles(13)
• Stage 0 tangles - "sparse, granular cytoplasmic immunoreactivity, without fibrillary structure, within otherwise morphologically normal pyramidal neuronal somas."
• Stage 1 tangles - "delicate, fibrillar- or rod-shaped tau2+ inclusions within neuronal somas."
• Stage 2 tangles - "classic, large, globose or flame-shaped tau2+ inclusions within neuronal somas."
• Stage 3 tangles (ghost tangles) - "large, acellular bundles of loosely arranged filaments located free in the neuropil."
• Stage 2 tangles seem to appear most frequently in AD brains, representing about 52% of tangles. (13)

 

The above image comes from Sheng et al. (1997) is as follows, "Photomicrographs of hippocampal tissue sections dual-immunolabeled either for tau2 (red) and S100B (Brown (left column): or for tau2 (red) and IL-1alpha (brown) (right column). IL-1alpha+microglia (arrows) and S100B+ astrocytes (arrows) are associated with tau2+ tangles representing each of the 4 defined stages of tangle formation. N= normal neurons without discernible tau immunoreactivity; So= neurons with stage 0 tangles; S1= neurons with stage 1 tangles; S2- neurons with stage 2 tangles; S3= extracellular stage 3 tangles. Bar= 10u." For more information on this subject, or about this particular picture, please see the web address below under Sheng et al., 1997.

• Senile plaques are mostly considered to be cellular deposits that are mostly composed of insoluble B-amyloid protein (AB). (6)
• All individuals with AD have these plaques that connect with dying nerve endings. (12)
• The greater the number of plaques in the cognitive regions of the brain, the greater the mental impairment.(12)
• Individuals with Down Syndrome often develop these senile plaques by the age of 12.(12)
• Down syndrome patients usually get the typical AD brain pathology by the age of 50. This is caused by too great a production of AB, starting at birth. This accumulation of AB fibrils in the cerebral cortex seems to be an early event in AD and come before other lesions in the brain as well as before clinical symptoms appear. (11)

• Microglial Cells are the main cells of the brain's immune system, which are activated in AD. (2)
• If microglial cells were significant in the process of AD, then there is the expectation that vulnerable regions in the brain (vulnerable to AD) would also exhibit greater microglial cell activation.(2)
• Research has found that older, dementia individuals have significantly more microglial activation than older, non-dementia individuals, who in turn have a slight increase of microglial activation than younger, non-dementia individuals.(2)

• The amyloid beta peptide is a molecule that is spread within the higher centers of the AD brain. (9)
• Amyloid Beta Peptideis the solution form changes what is considered normal functions of the neurons and glial cells in the brain.(9)
• Proteins found accompanying the amloid beta peptide deposits are: (9)
• alpha1-antichymotrypsin
• apolipoprotein E (APOE)

• complement peptides

• Early onset of familial AD has been connected with presenilins 1 and 2 (PS1 and PS2). (14)
• When PS1 or PS2 are overexpressed, the genes seem to develop abnormal cleaved spots at unusual sites.(14)
• These cleaved areas could help to produce cells that are susceptible to apoptosis (programmed cell death) which is linked to AD.

• Nitric Oxide (NO) has been implicated in AD as it helps to cement memories. (15)
• NO Synthase (NOS) makes NO but can cause problems in the brain if too much or too little is produced. (15)
• NO can (in abnormal proportions) destroy healthy tissue in the brain, bowels, and joints which can lead to neurodegenerative and inflammatory diseases.(15)

• Energy metabolism has been found to be especially low in the brains of those with AD. (1)
• These individuals with low metabolism levels have high levels of a mutant cytochrome oxidase (CO) which (in its normal state) is an enzyme that helps to produce energy. (1)

• Estrogen is a possible cure, or weapon, against AD. (16)
• Estrogen is a hormone that protects neurons. (16)
• Richard Mayeux of Columbia College of Physicians and Surgeons in New York City followed 1124 elderly women for 1 to 5 years. When the study ended, 6% of the women taking estrogen had developed AD where 16% of those not taking estrogen had developed AD. Further studies are on the way. (16)

For more information on the research that is being done on Alzheimer's disease, please visit The Alzheimer's Research Forum Homepage at http://www.alzforum.org/members/index.html

References

1. Barinaga, M. (1997). Neuroscience: A mitochondrial Alzheimer's Gene? Science, May 2; 276: 682 (in Research News.)
2. Dipatre, P. L., & Gelman, B. B. (1997). Microglial cell activation in aging and Alzheimer disease: Partial linkage with neurofibrillary tangle burden in the hippocampus. The Journal of Neuropathology and Experimental Neurology, February. Reproduced at http://www.alzforum.org/members/research/neuro/dipat/index.htm
3. Holden, C. (ed.) (1997). Boxer genes. Science, July 18; 277: 321 (in Random Samples.)
4. Jasny, B. R. (1995). In transition. Science, October 20; 270: 359 (in Editorial.)
5. Marshall, E. (1997). Alzheimer's maverick moves to industy. Science, June 27; 276: 1962 (in News & Comments.)
6. Meda, L., Cassatella, M. A., Szendrel, G. I., Otvos, L. Jr., Baron, P., Villalba, M., Ferrari, D., & Rossi, F. (1995). Activation of microglial cells by B-amyloid protein and interferon-y. Nature, 374: 647-650.
7. Microsoft ® Encarta ® 97 Encyclopedia. (1997). Alzheimer's Disease. © 1993-1996 Microsoft Corporation.
8. Pennisi, E. (1997). Immune gene ties to Alzheimer's. Science, September 5; 277: 1441 (in Random Samples.)
9. Robert S. Haldeman Laboratory for AD Research. (Found 9/13/97). The Robert S. Haldeman laboratory for Alzheimer's research. Found at http://www.public.asu.edu/~flaco/ad2.html
10. Rowe, J. W. (1997). The new gerontology. Science, October 17; 278: 367 (in Editorial.)
11. Selkoe, D. (1997). Alzheimer's Disease: Genotypes, phenotype, and treatments. Science, January 31; 275: 630-631 (in Perspectives.)
12. Selkoe, D. (Found 10/16/97). Online forums: Fifth International Conference - "The Amyloid Hypothesis". Found at http://www.alzforum.org/members/forums/selkoe/seminar/index.html
13. Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1997). Glial-neuronal interactions in Alzheimer Disease: Progressive association of IL-1alpha+ microglia and S100B+ astrocytes with neurofibrillary tangle stages. The Journal of Neuropathology and Experimental Neurology, March. Reproduced at http://www.alzforum.org/members/research/neuro/sheng/index.htm
14. Szuromi, P. (ed.) (1997). Apoptosis and Alzheimer's. Science, July 18; 277: 289 (in This Week in Science.)
15. Wickelgren, I. (1997). Biologists catch their first detailed look at NO enzyme. Science, October 17; 278: 389 (in Research News.)
16. Wickelgren, I. (1997). Estrogen: A new weapon against Alzheimer's. Science, May 2; 276: 676-677.

To visit the journal Science please visit http://www.sciencemag.org

This page hosted by Get your own Free Home Page