Article

The Genetics of Alzheimer Disease: Current Status and Future Prospects

Harvard University, Cambridge, Massachusetts, United States
JAMA Neurology (Impact Factor: 7.01). 03/1998; 55(3):294-6. DOI: 10.1001/archneur.55.3.294
Source: PubMed

ABSTRACT Four genes involved in the development of Alzheimer disease have been identified. Three fully penetrant (deterministic) genes lead to the development of Alzheimer disease in patients younger than 60 years: the amyloid beta-protein precursor on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1. Together, they account for about half of this early-onset form of the disease. One genetic risk factor--apolipoprotein E-4--is associated with late-onset Alzheimer disease. It accounts for a substantial fraction of disease burden but seems to act primarily to lower the age of disease onset. In general, none of these genes can be easily adapted for use as a diagnostic or predictive test for Alzheimer disease. Research activity includes searching for additional genes, especially for late-onset disease, and elucidating the mechanism of action of all identified genes as part of a long-term effort to develop more effective therapeutic and preventive strategies.

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    • "Less common mutations are found in the gene for valosin-containing protein (VCP) on 9p21-12 [18], in the gene coding for TDP-43 [19], in the gene for charged multivesicular binding protein 2B (CHMP2B) [20], and in the fused-in-sarcoma (FUS) gene on chromosome 16 [21], but there still remain cases with as yet unidentified genetic defects. Regarding age of onset of FTD, FUS gene mutations have been associated with age of onset ≤40 years of age [21]; on the other hand, early onset cases of alzheimer disease (AD) have been reported to be associated with mutations in the genes encoding for presenilin 1 (PS1) on chromosome 14, presenilin 2 (PS2) on chromosome 1, and the amyloid βprotein precursor (APP) on chromosome 21 [13]. FTD in a remarkably young patient has to be diagnosed with caution. "
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    ABSTRACT: Tardive dystonia is a serious extrapyramidal side effect emerging after long-term treatment with antipsychotics, frequently with a deteriorating course, and unsatisfactory treatment. Presently, clozapine is used for the cotreatment of tardive dystonia and psychosis, at the cost of serious side effects. Apart from clozapine, there have been case reports describing positive effects of quetiapine on dystonic symptoms. Aim of the present study was to demonstrate the ameliorating effects of quetiapine on dystonic symptoms, in a sample of patients suffering from antipsychotic-induced tardive dystonia. Quetiapine was administered to 16 consecutively enrolled stabilized patients with psychotic or mood disorders and tardive dystonia, replacing the "offending drugs," over a 3-month cross-tapering period. Target dose of quetiapine was set according to the defined daily dose of the received antipsychotic(s) at baseline, as reviewed by the World Health Organization Center of Drug Statistics Methodology, aiming at both maintenance of psychosis control and reduction of dystonic symptoms. Patients were found to have significant positive results in amelioration of dystonia (P < 0.001) over a 1-year period, without loss of antipsychotic efficacy. Reduction of dystonic symptoms with the use of quetiapine could be considered comparable with the positive effects of clozapine, with the additional advantage of relatively lacking serious side effects. Quetiapine may represent a valuable therapeutic choice for the treatment of tardive dystonia.
    Clinical neuropharmacology 07/2015; 38(4). DOI:10.1097/WNF.0000000000000086 · 1.84 Impact Factor
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    • "Part of the control group consisted of family members of AD patients. This may have caused a selection bias, since family history is a risk factor for AD [Blacker and Tanzi, 1998]. Furthermore, no follow-up information is available for the control group. "
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    Human Brain Mapping 05/2014; 35(5). DOI:10.1002/hbm.22335 · 6.92 Impact Factor
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    • "Genetic factors such as Apolipoprotein E (APOE) genotype might influence EOAD and LOAD forms. The presence of the APOE ε4 allele is a risk factor for LOAD (Blacker and Tanzi, 1998; Meyer et al., 1998) and has been suggested to modulate the disease onset and expression (van der Flier et al., 2011; Wolk et al., 2010). In EOAD, conversely, other genes such as APP, PSEN1, and PSEN2 (Raux et al., 2005; Rovelet-Lecrux et al., 2006) could be involved. "
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