Emma L. Jones

Background/Aims: Cognitive impairment is a well-established correlate of psychotic symptoms in Alzheimer’s disease (AD-P). We review whether this relationship has confounded previous genetic association studies of 5HTTLPR and AD-P. Methods: We reviewed all studies on 5HTTLPR and conducted a semi-quantitative analysis. Results: Three out of 4 studies with low MMSE reported a significant association, while 1 out of 4 with high MMSE reported a significant association. Conclusions: Variation in cognitive impairment in past studies has contributed to the inconsistency in findings. The findings presented here bring a greater clarity to our understanding of the role of 5HTTLPR in AD-P.

Post-operative cognitive decline is frequent in older individuals following major surgery; however, biomarkers of this decline are less clearly defined. Sixty-eight participants over the age of 60 provided blood samples at baseline and 24 h post-surgery. Cognitive decline was measured at baseline and 52 weeks post-surgery using the Cambridge Assessment for Mental Disorder in the Elderly, section B (CAMCOG) score. Plasma levels of neuron-specific enolase (NSE) and S100B were measured by ELISA. Baseline NSE and the change in NSE levels between baseline and 24 h were correlated with the change in CAMCOG score between baseline and 52 weeks. NSE concentrations may be a useful predictor of individuals at risk of more severe long-term cognitive decline.

Background: DYRK1A is a kinase targeting several proteins associated with the pathology of dementias, including α-synuclein and amyloid precursor protein. It is not clear if DYRK1A genetics are associated with neurodegenerative conditions. Objective: To determine if DYRK1A also has a genetic association with α-synuclein dementias such as dementia with Lewy bodies and Parkinson’s disease dementia. Methods: DNA samples from prospectively followed cohorts of control and dementia individuals were genotyped for the DYRK1A rs8126696 polymorphism. Results: The rs8126696 polymorphism altered the risk of developing an α-synuclein-associated dementia. Conclusion: DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia.

Background/Aims: Genetic risk factors have not been clearly established for vascular dementias (VaD) related to stroke and cerebrovascular disease. Methods: Samples were genotyped for APOE, MTHFR and ICAM. Aβ levels and choline acetyltransferase (ChAT) activities were assayed in controls and individuals with VaD. Results: Associations were found between the APOE-Ε4 allele and mixed dementia, infarct/stroke dementia and subcortical ischemic vascular dementia (SIVD), and higher Aβ1-42 levels and decreased ChAT activity. MTHFR was more associated with SIVD, mixed dementia, and lower ChAT activity. Conclusions: The study demonstrates important differences in the genetic associations of VaD and begins to clarify the genetic basis of key pathological substrates.

People with Down syndrome (DS) develop Alzheimer′s disease (AD) with an early age of onset. A tetranucleotide repeat, attt₅₋₈, in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study. The authors examine the impact of this polymorphism in a larger cohort of individuals with DS. Adults with DS were genotyped for attt₅₋₈ and APOE. The results were analysed with respect to the age of onset of dementia. The presence of three copies of the six‐repeat allele resulted in onset of dementia seven years earlier than in the presence of other genotypes. Further study is essential to elucidate the mechanism by which this polymorphism functions, with an exciting opportunity to identify novel treatment targets relevant for people with DS and AD.

Background/Aims: Most people with Down syndrome (DS) develop Alzheimer’s disease (AD). The extended tau haplotype has been linked to AD. In this study, we examined the haplotype’s effect on the age of onset of AD in DS. Methods: People with DS were assessed for dementia. Genotyping was performed for the extended tau haplotype, APOE anda polymorphism in APP, attt5–8. Results: Haplotype frequencies vary between those developing AD before 45 and those developing dementia after this age (p = 0.03). H1/H2 individuals are more likely to develop dementia before 45 than H1/H1 individuals (OR = 3, 95% CI = 1.01–8.91). Conclusion: Even in a condition driven by excess amyloid pathology, factors affecting tau are also important and should be considered as potential treatment targets.