Dementias genetics

The genetics of Lewy body dementia remains largely uncertain 659... 

Sleegers, K., Roks, G., Theuns, J. etal. Familial clustering and genetic risk for dementia in a genetically isolated Dutch population. Brain 127 1641-1649, 2004. 

Wilhelmsen, K. C., Lynch, T., Pavlou, E., Higgins, M. and Nygaard, T. G. Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21-22. Am. J. Hum. Genet. 55 1159-1165,1994. 

Bertram, L. and Tanzi, R. Genetics of Alzheimer s disease. In D. Dickson (ed.), Neurodegeneration- The Molecular Pathology of Dementia and Movement Disorders. Basel ISN Neuropathology Press, 2003, pp. 40-46. 

See also research, medical biochemical individuality and, 206-207 metabolism, 203 variations, exceptions and, 202 vision, 202-203 vitamin research and, 204-205 scopolamine, 228 scurvy, 167-168 self-esteem, genetics and, 16 self-selection of foods, 180 Selye, Hans, 230 senile dementia, 34-35, 227, 230 sensory physiology and psychology, 205 serotonin, 236 serum amylase, 80-81 serum lipase, 81 serum phenol sulfatase, 81 sex behavior, 100, 104-105 psychiatry and, 231 sex differences... 

Guyant-Marechal L, Verrips A, Girard C, Wevers RA, Zijlstra F, et al. 2005. Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype. Am J Med Genet A 139 114-117. 

Fig. 10.8 Absolute genetic variation (AGV) and relative genetic variation (RGV) between Alzheimer s disease and vascular dementia associated with bigenic, trigenic, and tetragenic clusters of Alzheimer s disease (AD)-related genes. APOE, apolipoprotein E PS, presenilin. (Adapted from refs. 12,19,20, and 59.)...

Cardiovascular and cerebrovascular disorders associated with lipid metabolism disturbance and atherosclerosis represent major risk factors for dementia (3,25,59). Atherosclerosis is the primary cause of heart disease and stroke in which genetic and environmental factors converge (553). More than 90% of patients older than 70-80 yr with dementia show signs of atherosclerosis in their arteries and a clear cerebrovascular component in their dementia process. It is very likely that pure AD is practically absent in octogenarians, in whom the prevalent diagnosis is vascular or mixed dementia (3,25,59), in which the APOE-4 allele also accumulates (18-20,554). 

Cacabelos, R. (1999) Textbook of neurogerontology and neurogeriatrics. Alzheimer disease and other dementias. /. Epidemiology and genetics, Masson, Barcelona. 

Reiman, E.M., Chen, K., Alexander, G.E., et al. (2004) Eunctional brain abnormaUties in young adults at genetic risk for late-onset Alzheimer s dementia. Proc. Natl. Acad. Sci. U. S. A., 101, 284-289. 

Tysoe, C., Galinsky, D., Robinson, D., et al. (1997) Analysis of alpha-1 antichymotrypsin, presenilin-1, angiotensin-converting enzyme, and methylenetetrahydrofolate reductase loci as candidates for dementia. Am. J. Med. Genet., 74, 207-212. 

Zuliani, G., Ble, A., Zanca, R., et al. (2001) Genetic polymorphisms in older subjects with vascular or Alzheimer s dementia. Acta Neurol. Scand., 103,304-308. 

The cause of Alzheimer s disease is unknown, but genetic factors clearly play a role. One clue supporting this view is provided by the observation that individuals with Down syndrome, a common cause of mental retardation, frequently develop a dementia similar to Alzheimer s disease during early adulthood. Vascular dementia, which is also called multi-infarct dementia, results from the accumulation of tiny strokes. Individually, these strokes or infarcts are too small to cause any noticeable problem, but as they accumulate, they produce deficits similar to Alzheimer s disease. Other neurological diseases such as Parkinson s disease, Pick s disease, and Huntington s disease cause slow deterioration of the brain that ultimately leads to a degenerative dementia. 

Although chelation is not helpful for Alzheimer s disease patients, it is the key to treating patients with dementia due to Wilson s disease. Wilson s disease is a genetically inherited disorder that usually strikes before age 30. The disease causes toxic levels of copper to accumulate in the liver, brain, eyes, and kidney. Untreated, Wilson s disease leads to tremors, cirrhosis, depression, psychosis, dementia, and ultimately death. Chelation with penicillamine (Cuprimine) can stop and even reverse the accumulation of copper. 

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