Linkage to chromosome 14q in Alzheimer's disease (AD) patients without psychotic symptoms

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
Dimitrios AvramopoulosSusan S Bassett

Abstract

Cases of early onset AD have been attributed to three genes, PSEN1, PSEN2, and APP, while the only gene consistently associated with late onset AD (LOAD) is APOE. Several genome scans have now been performed for LOAD with inconsistent findings in several genomic regions, possibly reflecting the underlying genetic heterogeneity. Many lines of evidence suggest that the absence or presence of psychotic symptoms, common in AD, might delineate distinct etiologic disease subtypes. We have performed a genome scan of 148 AD pedigrees (ages of onset more than 50 years) including the presence or absence of delusions and hallucinations as covariates. This approach identified linkage to a locus on chromosome 14q24.3, close to the PSEN1 locus (LOD score 3.91; genome-wide empirical P = 0.052), derived from individuals that do not have co-morbid hallucinations. The finding appears stronger (LOD score 5.74; genome-wide empirical P = 0.048) in families that include younger affected members (AAO between 50 and 65 years), however it is not present without the inclusion of the covariate and we observe no correlation between the presence of hallucinations and the age of onset. A mutation screen of PSEN1 did not detect any coding region or splice si...Continue Reading

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