Browsing by Subject "Arteriolosclerosis"

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    Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe
    (IOS Press, 2016) Nho, Kwangsik; Saykin, Andrew J.; Nelson, Peter T.; Department of Radiology and Imaging Sciences, IU School of Medicine
    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.
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    Using digital pathology to analyze the murine cerebrovasculature
    (Sage, 2024) Niedowicz, Dana M.; Gollihue, Jenna L.; Weekman, Erica M.; Phe, Panhavuth; Wilcock, Donna M.; Norris, Christopher M.; Nelson, Peter T.; Neurology, School of Medicine
    Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and cross-reactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed sections. A panel of immunohistochemical blood vessel markers were tested (including CD31, CD34, collagen IV, DP71, and VWF), to evaluate their suitability for digital pathological analysis. Collagen IV provided the best immunostaining results in both FFPE and frozen fixed murine brain sections, with highly-specific staining of large and small blood vessels and low background staining. Subsequent analysis of collagen IV-stained sections showed region and sex-specific differences in vessel density and vessel wall thickness. We conclude that digital pathology provides a useful tool for relatively unbiased analysis of the murine cerebrovasculature, provided proper protein markers are used.