Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) accumulation and brain atrophy; however, the assocation between plasma Aβ biomarkers and regional neurodegeneration remains unclear. We inve Show more
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) accumulation and brain atrophy; however, the assocation between plasma Aβ biomarkers and regional neurodegeneration remains unclear. We investigated whether plasma Aβ42, Aβ40, and the Aβ42/40 ratio are associated with temporal lobe atrophy measured using tensor-based morphometry (TBM) in cognitively healthy controls (HC) and participants with mild cognitive impairment (MCI). We analyzed longitudinal MRI and plasma biomarkers data from 29 participants from ADNI (HC = 14, MCI = 15) with imaging and blood samples available at baseline, 24 months, and 48 months. TBM Jacobian maps were summarized within temporal lobe regions of interest (ROIs). Associations between plasma Aβ measures and TBM-derived atrophy were examined with linear mixed-effects models, adjusting for age, sex, and APOE ε4 status, with false-discovery-rate correction. Participants with MCI showed greater temporal lobe atrophy compared with HC people, with significantly lower TBM values at follow-up. Plasma Aβ42, Aβ40, and Aβ42/40 levels showed no consistent or robust differences between diagnostic groups. After covariate adjustment and FDR correction, no plasma Aβ-TBM associations were significant at baseline or 24 months. At 48 months, positive associations were identified between Aβ42 and temporal lobe atrophy (measure 2) in HC participants (β = 0.70, p = 0.046) and between Aβ40 and measure 2 in participants with MCI (β = 0.60, p = 0.036). In contrast, a negative association was observed between the Aβ42/40 and temporal lobe atrophy (measure 2) in MCI group (β = -0.53, p = 0.049). TBM captured greater temporal lobe atrophy in participants with MCI compared with HC. Plasma amyloids showed only limited and inconsistent associations with temporal lobe atrophy over time. These findings suggest that plasma Aβ measures alone may not reliably reflect longitudinal regional neurodegeneration in early AD. Show less
Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic fami Show more
Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned. Show less