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[O1–04–01]: RACIAL DISPARITIES IN COGNITIVE AGING TRAJECTORIES IN LARGE LONGITUDINAL STUDIES IN NEW YORK AND CHICAGO
Author(s) -
Zahodne Laura B.,
Barnes Lisa L.,
Gross Alden L.,
Bennett David A.,
Mayeux Richard,
Manly Jennifer J.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.051
Subject(s) - cognition , gerontology , cognitive decline , health equity , socioeconomic status , cognitive test , cohort , longitudinal study , psychology , demography , health and retirement study , race (biology) , medicine , dementia , population , sociology , public health , psychiatry , nursing , disease , gender studies , pathology
were screened against older, autopsy-confirmed pure AD controls (age > 85 years, n1⁄4274) and clinically-defined healthy controls (age > 80 years, n1⁄44572). Variants seen in at least two dual path cases and none of the older, pure AD controls or healthy controls were examined further. For the remaining variants, we searched other neurodegenerative exome databases to determine their specificity to mixed AD/DLB pathology. For our top variant we performed immunohistochemical staining of autopsy-confirmed AD/DLB mixed pathology brain tissue. Finally, we explored potential functional effects of the variant by examining gene expression in post-mortem temporal cortex RNA-seq data fromADcases (n1⁄482) and controls (n1⁄480). Results: The initial screening process yielded eleven variants present in at least two dual pathology cases and none of the healthy controls or older pure AD cases. Of these, we focused on rs76938320-A (NP_001138468.1:p.Ser700Leu, MAF1⁄40.0002) on exon 18 of ITGA7 because of its predicted probable damaging effect using in silico prediction tools, its presence in three younger AD cases (age < 80 years) in ADSP, its high frequency in the ALS exome database, and the finding of a homozygous carrier with TDP43 and tau pathology. ITGA7 transcript isoforms that contain exon 18 show significantly higher expression in AD temporal cortex tissue when compared to controls (P < 0.001) in the Mayo Clinic Transcriptomics data set. Immunohistochemical staining of AD, AD/DLB, DLB, and vascular dementia brain tissue suggest that AD and AD/DLB tissue express higher levels of ITGA7 than vascular controls and pure DLB. Conclusions: Convergent data from exome sequencing, immunohistochemical stains, and transcriptomic analysis suggest that this ITGA7 variant may predispose not only to mixed AD/DLB pathology but to the development of multiple proteinopathies.