Nevertheless, the apoprotein E??2 variant may be confer a delay in onset or severity of Alzheimer’s disease in adults with Down syndrome [55]. The amyloid hypothesis and its appealing simplicity in the framework of overproduction blog post versus reduced clearance, and the identification of some of the genes responsible for these processes, opens the door for genetic or downstream intervention to prevent the onset of the disease. However, no treatments used in adults with Down syndrome and dementia have yet been shown to prevent or ameliorate the onset of Alzheimer’s disease. Only a minority of people with familial early-onset disease have APP gene mutations, but models of the processes involved in the discovery of treatments for Alzheimer’s disease in people with Down syndrome, such as the amyloid hypothesis, will probably be of benefit in the search for treatments for people with familial early-onset Alzheimer’s disease.

Conclusion The study of Alzheimer’s disease in individuals with Down syndrome has assisted in the understanding of early-onset Alzheimer’s disease in many ways, but not enough to provide a basis for successful treatment or prevention of dementia. First, there was the recognition of the homology of the damaging amyloid protein in the brains of individuals with Down syndrome and Alzheimer’s disease and of that in those with early-onset Alzheimer’s disease. The protein was further shown to derive from cleavage from an APP. Then there was the postulation that the gene encoding APP was situated on chromosome 21, which was later proved.

Although few adults with early-onset Alzheimer’s disease necessarily had mutations or isolated trisomy of the APP gene, features and processes that somehow impaired the metabolism of APP and would result in its excessive production were sought and discovered. A second component of the Alzheimer disease neuropathology, the neurofibrillary tangles from tau hyperphosphorylation, has been hypothesised in adults with Down syndrome to be at least partly due to another gene on chromosome 21 – DYRK1A, a gene that encodes Batimastat a protein kinase enzyme which promotes tau hyperphosphorylation. As a result of these studies, the hypothesis that Alzheimer’s disease was fundamentally due to an imbalance of production and clearance of toxic forms of amyloid and tau proteins was made.

The simultaneous development of gene technology and using the amyloid hypothesis led to the discovery of many mutations in other genes causing early-onset Alzheimer’s disease. For people with Down syndrome and Alzheimer’s disease and for those Tofacitinib Citrate msds with early-onset Alzheimer’s disease, a common problem is the overproduction of the toxic deposits. To date, the majority of genetic defects in familial early-onset Alzheimer’s disease result in mechanisms leading to overproduction of the amyloid protein rather than mechanisms causing tau hyperphosphorylation.