Vol 5 n° 1 - Dementia
Past issues Contributors How to publish Contributions and comments Home
 
n 1907, Alois Alzheimer, a Bavarian psychia- trist, reported the case of a middle-aged woman who developed progressive memory loss and cognitive dis- orders with autopsy findings of neuritic plaque and neuro- fibrillary tangles in the cerebral cortex.1 Thereafter, it was named as Alzheimer’s disease (AD). However, it was only in the 1960s that came to be recognized as the most common cause of dementia in the aged.2 AD cur- rently  accounts  for  at  least  60%  to  70%  of  cases  of dementia in aged people.3 In the United States, the total prevalence of AD is greater than 2.3 million and poten- tially affects more than 4 million individuals.4 The aver- age duration of AD is 8 to 10 years, or even shorter.AD has been ranked as the fourth leading cause of death in the United States.2 By the year 2025, over 22 million patients with dementia are expected around the world.5,6 Pathology of AD The pathologic criteria for diagnosis of AD require the presence of both neuritic plaques and neurofibrillary tan- gles, together with a progressive decline in cognitive func- tion.7 The neuritic plaques are composed of aggregations of b-amyloid (Ab) and are surrounded by dystrophic neu- rons and astrocytes.8-10 The neurofibrillary tangles consist of intraneuronal aggregations of hyperphosphorylation microtubule–associated  protein  tau.11-14  Reduction  in synaptic density and neuronal loss in some specific brain regions, including the cerebral cortex and hippocampus, are  also  important  criteria  in  the  diagnosis  of AD.15-19 Clinically,AD is rarely found in people under the age of B a s i c   r e s e a r c h 1 7 Genetic studies in Alzheimer’s disease Ya-Ping Tang, MD, PhD; Elliot S. Gershon, MD I Keywords:  genetics;  Alzheimer’s  disease;  APOE;  APP;  PS1;  PS2;   -amyloid; apolipoprotein E; amyloid precursor protein Author  affiliations:  Department  of  Psychiatry,  The  University  of  Chicago, 5841 S Maryland Avenue, Chicago, Ill, USA Address  for  correspondence:  Ya-Ping  Tang,  MD,  PhD,  Department  of Psychiatry, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
(e-mail: yptang@delphi.bsd.uchicago.edu) Alzheimer’s disease (AD), the most common cause of dementia in aged populations, is believed to be caused by both  environmental  factors  and  genetic  variations. Extensive linkage and association studies have established that a broad range of loci are associated with AD, includ- ing both causative and susceptibility (risk factor) genes. So far, at least three genes, APP, PS1, and PS2, have been identified as causative genes. Mutations in these genes have been found to cause mainly early-onset AD. On the other hand, APOE has been identified to be the most common  high  genetic  risk  factor  for  late-onset  AD. Polymorphisms in the coding region, intron, and pro- moter region of certain genes constitute another kind of genetic variation associated with AD. A number of other genes or loci have been reported to have linkage with AD, but many show only a weak linkage or the results are not well reproduced. Currently, the measurable genetic asso- ciations account for about 50% of the population risk for AD. It is believed that more new loci will be found to asso- ciate with AD, either as causative genes or genetic risk fac- tors, and that eventually the understanding of genetic factors in the pathogenesis of AD will be important for our efforts to cure this illness. Dialogues Clin Neurosci. 2003;5:17-26.