Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Diabetic Retinopathy ; complications ; epidemiology ; physiopathology ; Humans ; Neurodegenerative Diseases ; epidemiology ; etiology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Risk Factors

Subjective memory impairment (SMI) is now increasingly recognized as a risk factor of progression to dementia. This study investigated gray and white matter changes in the brains of SMI patients compared with normal controls and mild cognitive impairment (MCI) patients. We recruited 28 normal controls, 28 subjects with SMI, and 29 patients with MCI aged 60 or older. We analyzed gray and white matter changes using a voxel-based morphometry (VBM), hippocampal volumetry and regions of interest in diffusion tensor imaging (DTI). DTI parameters of corpus callosum and cingulum in SMI showed more white matter changes compared with those in normal controls, they were similar to those in MCI except in the hippocampus, which showed more degenerations in MCI. In VBM, SMI showed atrophy in the frontal, temporal, and parietal lobes compared with normal controls although it was not as extensive as that in MCI. Patients with SMI showed gray and white matter degenerations, the changes were distinct in white matter structures. SMI might be the first presenting symptom within the Alzheimer's disease continuum when combined with additional risk factors and neurodegenerative changes.
Aged ; Brain/*pathology ; Diagnosis, Differential ; Diffusion Tensor Imaging/methods ; Female ; Gray Matter/*pathology ; Humans ; Male ; Memory Disorders/*diagnosis/etiology ; Mild Cognitive Impairment/complications/*diagnosis ; Neurodegenerative Diseases/complications/*pathology ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; White Matter/*pathology

Our study was performed to determine whether cardiac autonomic neuropathy can predict deterioration of the renal function in normoalbuminuric, normotensive people with type 2 diabetes mellitus (DM). One hundred and fifty-six normoalbuminuric, normotensive people with type 2 DM were included in our retrospective longitudinal study. We categorized normal patterns, early patterns, and definite or severe patterns according to the results of the cardiac autonomic function test. Of 156 patients included, 54 had normal patterns, 75 had early patterns, 25 had definite or severe patterns, and 2 had atypical patterns. During a median follow-up of nine years, glomerular filtration rates (GFR) remained stable in the normal and early pattern groups (mean changes, 4.50% and 0.77%, respectively) but declined in those with definite or severe patterns (mean change, -10.28%; p=0.047). An abnormal heart response to the deep breathing test of the cardiac autonomic function tests was an independent predictor of GFR decline. Our data suggest that cardiac autonomic neuropathy, especially with a definite or severe pattern, might be associated with a subsequent deterioration in renal function in normoalbuminuric, normotensive people with type 2 DM.
Aged ; Blood Pressure ; Diabetes Complications ; Diabetes Mellitus, Type 2/*diagnosis/*pathology ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Heart Diseases/*complications ; Heart Rate ; Humans ; Kidney/*pathology ; Kidney Diseases/*therapy ; Male ; Middle Aged ; Nephrology/methods ; Neurodegenerative Diseases/*complications

Marchiafava-Bignami disease (MBD) is a rare alcohol-related disorder that results in progressive demyelination and necrosis of the corpus callosum. The process may extend to the optic chiasm and tracts, cerebellar peduncle, subcortical resion, neighboring white matter, and rarely, cortical gray matter. We report a case of MBD in which fluid-attenuated inversion recovery and diffusion magnetic resonance imaging studies revealed symmetrical hyperintense lesions in the cerebral cortex in addition to the callosal lesions.
Alcoholism/complications ; Brain/pathology ; Cerebral Cortex/*pathology ; Corpus Callosum/*pathology ; Demyelinating Diseases/pathology ; Diffusion Magnetic Resonance Imaging/methods ; Humans ; Male ; Marchiafava-Bignami Disease/*diagnosis/*pathology/*therapy ; Middle Aged ; Necrosis/pathology ; Neurodegenerative Diseases/pathology ; Optic Chiasm/pathology ; Seizures ; Time Factors ; Treatment Outcome ; Vitamin B Complex/therapeutic use