Additional file 2: Figure S1. of Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer’s disease

Structural covariance networks from four seed regions in GG, GA, and A homozygotes. According to the case numbers, the actual T value in AA was 5.529, GA = 4.924, and GG = 6.4612. (BMP 7288 kb

Additional file 1: of Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer’s disease

Supplementary Tables S1–S13. (DOCX 67 kb

Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer’s Disease

<div><p>Background</p><p>Amyloid deposition and white matter lesions (WMLs) in Alzheimer's disease (AD) are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR) against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden.</p><p>Methods</p><p>Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr) in 8 cortical volumes-of- interests (VOIs). The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates.</p><p>Results</p><p>Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024), but not regional (r = 0.264, p = 0.223) AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004), superior medial- (r = 0.443, p = 0.034), and middle-prefrontal (r = 0.448, p = 0.032) regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019) and hippocampal volume (r = -0.469, p = 0.016) showed significant correlations while the prefrontal (r = -0.417, p = 0.043) or hippocampal volume (r = -0.422, p = 0.04) also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume.</p><p>Conclusions</p><p>BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD.</p></div

Data_Sheet_1_Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel.docx

<p>Objective: Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort (n = 593) of common focal non-lesional epilepsy patients.</p><p>Methods: The customized focal epilepsy gene panel (21 genes) was based on multiplex polymerase chain reaction (PCR) and sequenced by Illumina MiSeq platform.</p><p>Results: Eleven variants (1.85%) were considered as pathogenic or likely pathogenic, including seven novel mutations. There were three SCN1A (p.Leu890Pro, p.Arg1636Ter, and p.Met1714Val), three PRRT2 (two p.Arg217Profs^*8 and p.Leu298Pro), two CHRNA4 (p.Ser284Leu, p.Ile321Asn), one DEPDC5 (p.Val516Ter), one PCDH19 (p.Asp233Asn), and one SLC2A1 (p.Ser414Ter) variants. Additionally, 16 other rare variants were classified as unknown significance due to inconsistent phenotype or lack of segregation data.</p><p>Conclusion: Currently known focal epilepsy genes only explained a very small subset of focal epilepsy patients. This indicates that the underlying genetic architecture of focal epilepsies is very heterogeneous and more novel genes are likely to be discovered. Our study highlights the usefulness, challenges and limitations of using the multi-gene panel as a diagnostic test in routine clinical practice in patients with focal epilepsy.</p

Partial correlations between cortical volume and GM AV-45 SUVr in 30 patients.

<p>Partial correlations between cortical volume and GM AV-45 SUVr in 30 patients.</p

Illustration of automatic quantification of 3D white matter (WM) lesion burden.

<p>(1) Individual T1-weighted image were registered to the corresponding FLAIR images using a 12 degrees of freedom affine transformation. (2) To obtain the transformation matrix, the coregistered T1-weighted images were registered to the averaged customized group T1 template in MNI space. (3) The inverse transformation matrix from step 2 was applied to the AAL template to generate corresponding AAL volumes in each individual's 3D T1WI native space for later calculation of normalized 3D WM volume. (4) WM volume of interest (VOI) on FLAIR sequences (5) Transfer the white matter volume of interest to the corresponding T1 image. (6) 3D WM volume constructions.</p

Model of prefrontal brain reserve with related regional volumes, white matter lesions and amyloid pathological load.

<p>Model of prefrontal brain reserve with related regional volumes, white matter lesions and amyloid pathological load.</p

General characteristics of the Alzheimer's disease patients.

<p>General characteristics of the Alzheimer's disease patients.</p

Prefrontal regions showing brain reserve to amyloid burden or white matter lesion loads.

<p>Prefrontal regions showing brain reserve to amyloid burden or white matter lesion loads.</p

Diffusion Tensor Imaging Study of White Matter Damage in Chronic Meningitis

<div><p>Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.</p></div