Taub Institute: Genomics Core
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TaubCONNECT Research Perspectives:
July 2016

Alzheimer's Association International Conference (AAIC 2016)

Earlier this week, thousands of dementia researchers, clinicians, and care providers from around the globe gathered together in Toronto for the annual Alzheimer's Association International Conference (AAIC 2016). Each year, Taub faculty members travel to this event to share and learn of new research in the field, and to network with like-minded colleagues. Below are several highlights from Taub faculty participation at this year's conference (in random order):

Dr. Yaakov Stern initiated the first Professional Interest Area (PIA) on "Reserve, Resilience, and Protective Factors in Alzheimer's disease," and chaired the data blitz for this PIA, which focused on epidemiologic, clinical/neuropsychological, and neuroimaging/biomarker approaches to understanding reserve, with a major emphasis on potential underlying structural and functional brain mechanisms. This new, collaborative undertaking is as part of the AA's International Society to Advance Alzheimer's Research and Treatment (ISTAART), a professional society aimed at strengthening scientific knowledge through greater collaboration among researchers and clinicians with shared PIAs. Dr. Hwamee Oh also participated in this PIA.

Dr. Sandra Barral Rodriguez presented work done by she and Dr. Badri Vardarajan, as team members in the Alzheimer's Disease Sequencing Project (ADSP) Family Working Group, at a featured research session on the ADSP. Their work in this group is focused on the analysis of whole genome sequencing data generated from ethnically diverse families multiply affected by Late Onset Alzheimer's Disease (LOAD). Dr. Barral reported on the results obtained from whole genome sequencing performed on 111 multiethnic LOAD families, with admixture mapping also carried out on Hispanic pedigrees. These results suggest that both coding and non-coding rare variants influence LOAD susceptibility, and show the continued utility of family-based approaches. Variants identified are currently being validated using orthogonal technologies, and follow-up analyses are being conducted.

Badri N. Vardarajan, PhD, MS

Dr. Badri Vardarajan chaired a session on the Genetics of LOAD, which included his own presentation, "Whole Exome Sequencing in Healthy Elderly Apoe ε44 Subjects to Identify Protective Variants in Alzheimer's Disease." This study of Caribbean Hispanic families multiply affected by LOAD revealed a protective variant segregating with APOE ε4 carriers in three large families. To further increase power, Badri and colleagues are conducting sequencing on 200 unaffected APOE ε4 carriers from the same population. Identifying coding sequence variants in LOAD will facilitate the creation of tractable models for investigation of disease related mechanisms and potential therapies.

Dr. Adam Brickman presented a study that examined whether the presence of cerebral microbleeds, a marker of cerebral amyloid angiopathy (CAA), mediates the relationship between white matter hyperintensities (WMH) and estimated symptom onset in individuals with and without autosomal dominant mutations for AD from the Dominantly Inherited Alzheimer's Network (DIAN). Although there was some co-dependency between WMH and cerebral microbleeds, the observed increases in WMH among mutation carriers did not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.

Dr. Yian Gu presented a study on diet and hippocampal atrophy that was co-authored by multiple Taub faculty members. The study, "Mediterranean diet is associated with slower rate of hippocampal atrophy: a longitudinal study in cognitively normal older adults," showed that, compared to those with low adherence to a Mediterranean diet (MeDi), those with middle and high level of adherence to MeDi had slower rate of decline in hippocampal volume.

Dr. Hwamee Oh presented a study examining whether extraversion and neuroticism are related to the level of beta-amyloid (Aβ) deposition, a pathological hallmark of AD. Results suggest that extraversion, possibly through lifestyle factors, correlates with lower Aβ deposition and better memory functions in cognitively normal elderly. Neuroticism, however, was not associated with either Aβ deposition or cognitive performance. Future studies need to address a causal relationship between personality and the vulnerability to AD-related pathology.

Drs. William C. Kreisl and Seonjoo Lee each presented studies which, as described by the AAIC, evaluated changes in odor identification as an early predictor of cognitive decline, or of the transition to dementia, and compared it to two established biological markers for cognitive decline and dementia: brain amyloid PET imaging and thickness of the brain's cortex in areas important to memory. These studies were also featured on the CUMC Newsroom, and widely distributed by the media this week.

Aging and Dementia Fellow Dr. Anjali Patel presented on the "Prediction of Relapse Following Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations," co-authored by Drs. Davangere Devanand, Seonjoo Lee, Gregory Pelton, and others. Results suggest that, for patients with severe hallucinations, particularly auditory hallucinations, antipsychotic discontinuation may not be advisable because of high relapse risk.

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