TOMM40 intron 6 poly-T length,age at onset,and neuropathology of AD in individuals with APOE ɛ3/ɛ3

BackgroundThis study investigates the association between TOMM40 poly-T length, age at onset, and neuropathology in individuals with Alzheimer’s disease (AD) with the apolipoprotein E (APOE) ɛ3/ɛ3 allele.MethodsThirty-two presenilin 1 (PSEN1) mutation carriers with AD, 27 presenilin 2 (PSEN2) mutation carriers with AD, 59 participants with late-onset AD (LOAD), and 168 autopsied subjects from a community-based cohort were genotyped for TOMM40 intron 6 poly-T (rs10524523) length using short tandem repeat assays.ResultsAmong AD individuals with PSEN2 mutations, the presence of a long poly-T was associated with an earlier age at onset, whereas there were no such associations for subjects with PSEN1 mutations or LOAD. In community-based participants, the presence of a long poly-T was associated with increased neuritic tangles and a greater likelihood of pathologically diagnosed AD.ConclusionTOMM40 intron 6 poly-T length may explain some of the variation in age at onset in PSEN2 familial AD and may be associated with AD neuropathology in persons with APOE ɛ3/ɛ3.     

Are apparent associations between parental representations and psychosis risk mediated by early trauma?

OBJECTIVE: It was investigated whether the reported association between representations of parental rearing style and psychosis does not represent a main effect, but instead is a proxy indicator of the true underlying risk factor of early trauma. METHOD: In a general population sample of 4045 individuals aged 18-64 years, first ever onset of positive psychotic symptoms at 3-year follow-up was assessed using the Composite International Diagnostic Interview and clinical interviews if indicated. Representations of parental rearing style were measured with the Parental Bonding Instrument (PBI). RESULTS: Lower baseline level of PBI parental care predicted onset of psychotic symptoms 2 years later. However, when trauma was included in the equation, a strong main effect of trauma emerged at the expense of the effect size of PBI low care. CONCLUSION: The results suggest that associations between representations of parental rearing style and psychosis may be an indicator of the effect of earlier exposure to childhood trauma.