Nexus - 1205 - New Times Magazine-pages

Page Content (OCR)

it about Auguste D.'s brain samples that Alzheimer found so of some 650,000, discovered only one Alzheimer's case in over a striking and unusual? He noticed something in the slides that was decade. In contrast, in the worst-affected Norwegian municipali- extremely rare: gum-like clumps outside some cells and ties during the period 1974-1983, the median annual age-adjusted abnormal collections of proteins inside others; that is, plaques and Alzheimer's disease mortality rates were between 44 and 55 per tangles respectively. A fresh look at the recently rediscovered 100,000 for males and between 87 and 109 per 100,000 for Auguste D. slides confirms Alzheimer's claims. Her cortex females.’* These figures suggest that Alzheimer's disease is at displayed what are now accepted as the classic pathological signs least 1,000 times more common in the municipalities along the of the disease named after him: amyloid plaques and south and southeastern coasts of Norway than in Maracaibo, neurofibrillary tangles. Indeed, neurofibrillary tangles were Venezuela. Even within Norway itself, Alzheimer's mortality was described for the first time ever in this brain.” higher by a factor of 15 in some municipalities than in others dur- It is now well known that such plaques and tangles are formed ing this period. by the deposition of abnormal proteins, especially beta-amyloid Studies of temporal change in dementia incidence are expensive and tau. The risk of developing Alzheimer's disease, therefore, and complex and involve extensive fieldwork. As a result, they are rises and falls with the ability to prevent the formation and depo- rare. The best study probably comes from Lundy, Sweden," where sition of such proteins. This ability is, in part, genetic. The the entire population was medically examined several times apolipoprotein (APO) E4 allele plays a key role in promoting between 1947 and 1972. Interestingly, all levels of dementia were Alzheimer's disease because of the inefficiency with which those found to have decreased by the end of the period. This seems possessing this genetic aberration can unusual, since more recent studies conducted remove brain beta-amyloid and tau.* in the United States,'* England,” Australia,” Genetically, however, there is more to Canada” and Norway” all suggest that Alzheimer's disease than the APO E4 gene. Alzheimer's disease is becoming increasingly To date, four genes have been identified as common. playing a role in either early- or late-onset The great bulk of Two recent research projects have demon- Alzheimer's disease: beta-amyloid precursor protein, presenilin-1, presenilin-2, and strated that migration greatly influences the prevalence rates of dementia. Graves and evidence from apolipoprotein hee. Workers nave numerous...studies co-workers ctaplished that, imme pepanese inked most of these variants to familia mericans of King County, Washington early-onset Alzheimer's, but the APO E4 therefore supports a State, dementia was more common than in allele is a relatively common risk factor for strong link between Japan. In addition, the distribution of sub- leveloping late-onset Alzheimer's disease. oe types of dementia in Japanese Americans Considerable progress has been made in aluminium was found to be much more like that of interpreting the significance of such genetic consumption, North American and European Caucasians variants. To illustrate, mutations in the presenilin-1 gene seem associated with increased super-oxide production and greater vulnerability to amyloid beta peptide toxicity.'' Interestingly, mutations in the presenilin genes, which are linked to more than 40 per cent of all familial Alzheimer's cases, cause enhanced production of an abnormal form of beta-amyloid precursor protein.'* This protein is longer than normal, aggregates more rapidly, kills neurons in culture more than of Japanese residing in their homeland. As a result, Alzheimer's disease was more common and vascu- lar dementia less prevalent in Japanese Americans than might have been expected. A similar study conducted in Indianapolis and Ibadan, Nigeria, by Hendrie and co-workers™ established that Alzheimer's disease was more than twice as common in African Americans than in Nigerian Yoruba of the same gender and age ranges. In summary, globally and regionally Alzheimer's disease does not have a especially monomeric aluminium from drinking water, and an elevated incidence of Alzheimer's disease. effectively and precipitates random, relatively uniform spatial preferentially to form amyloid plaques. The same elongated pattern. It appears to be increasing faster than the population is protein also is produced as a result of mutations in the gene ageing and its incidence and prevalence are greatly affected by encoding beta-amyloid precursor protein. migration. In short, it shows none of the expected geographical characteristics of a primarily genetic disease. ECAINJIDARIRACAITAL \VADIATIARIC The great bulk of evidence from therefore supports a strong link between aluminium especially monomeric aluminium from drinking water, and an elevated incidence of ENVIRONMENTAL VARIATIONS There must be far more to Alzheimer's disease, however, than just genetics. There is no doubt the environment plays a key role in this illness. Multi-infarct dementia is common in Japan but Alzheimer's disease incidence seems to be much lower than in Europe." This is unlikely to be due to racial variables because, in China, vascular dementia predominates in Beijing and Alzheimer's disease in Shanghai.'* At the regional scale, spatial variations in the incidence and prevalence of Alzheimer's disease are far greater. Two hospital- based studies'* involving brain autopsies of every patient dying with dementia in Maracaibo, Venezuela, a city with a population KEY RISK FACTORS In their book Genome, Bishop and Waldholz** argue that: "..aberrant genes do not, in and of themselves, cause disease. By and large their impact on an individual's health is minimal until the person is plunged into a harmful environment." The signifi- cance of an aberrant gene therefore depends upon location and lifestyle; that is, on geography. The preceding review of the literature establishes that the "harmful environments" that increase the significance of inheritance of the APO E4 gene and other Alzheimer's-related genetic aberrations have two very important characteristics. They 34 = NEXUS numerous...studies consumption, Alzheimer's disease. www.nexusmagazi ne.com AUGUST - SEPTEMBER 2005